Serration pattern analysis enables to differentiate epidermolysis bullosa acquisita (EBA) from other pemphigoid diseases by only using direct immunofluorescence (DIF) microscopy on a skin biopsy. Serration pattern analysis is a learnable and inexpensive technique that can be implemented as routine diagnostic method.
Practice serration pattern analysis online
Pattern recognition is learnable and can be trained online here with DIF photos and an instruction video explaining the differences between linear n-serrated patterns and linear u-serrated patterns.
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Optimal technical requirements
Serration pattern analysis is not restricted by variation in technical laboratory procedures, transport mediums, and experience of the observers. Optimization could be achieved with the following methods:
- Biopsy transport: preferable saline, also possible with Michel’s medium or snap frozen in liquid nitrogen.
- Biopsy fixation: only partially embedding of biopsy specimen in OCT compound.
- Cryosections: 4µm or 6µm thickness.
- Microtome blade: (non-disposable) wedge-shaped microtome blade optimal, also possible with disposable microtome blades.
- Microscope: standard fluorescence microscope with dry lens of x400 magnification (x40 lens and x10 ocular).
- Observers: easy learnable for everyone; for dermatologists and pathologists or laboratory technicians. Practice serration pattern analysis with DIF photos online here.
- Photography: not required for analysis for routine diagnostics.
Please contact us at for any question regarding serration pattern analysis.
Literature about serration pattern analysis
- Vodegel RM, Jonkman MF, Pas HH, de Jong MC. U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases. British Journal of Dermatology 2004;151(1):112-118
- Buijsrogge JJ, Diercks GF, Pas HH, Jonkman MF.The many faces of epidermolysis bullosa acquisita after serration pattern analysis by direct immunofluorescence microscopy. British Journal of Dermatology 2011;165(1):92-98
- Terra JB, Pas HH, Hertl M, Dikkers FG, Kamminga N, Jonkman MF. Immunofluorescence serration pattern analysis as a diagnostic criterion in antilaminin-332 mucous membrane pemphigoid: Immunopathological findings and clinical experience in 10 dutch patients. British Journal of Dermatology 2011;165(4):815-822
- Terra JB, Meijer JM, Jonkman MF, Diercks GF. The n- vs. u-serration is a learnable criterion to differentiate pemphigoid from epidermolysis bullosa acquisita in direct immunofluorescence serration pattern analysis. British Journal of Dermatology 2013;169(1):100-105
- Terra JB, Jonkman MF, Diercks GF, Pas HH. Low sensitivity of type VII collagen enzyme-linked immunosorbent assay in epidermolysis bullosa acquisita: Serration pattern analysis on skin biopsy is required for diagnosis. British Journal of Dermatology 2013;169(1):164-167
- Meijer JM, Diercks GF, Schmidt E, Pas HH, Jonkman MF. Laboratory diagnosis and clinical profile of anti-p200 pemphigoid. JAMA Dermatology 2016;152(8):897-904
2016 Shi C, Meijer JM, Guo J, Azzopardi G, Jonkman MF, Petkov N. Automatic classification of serrated patterns in direct immunofluorescence images Autonomous Systems 2015 - Proceedings of the 8th GI Conference, Fortschritt-Berichte VDI pp 61–69.
- Shi C, Meijer JM, Guo J, Azzopardi G, Jonkman MF, Petkov N. Automatic classification of serrated patterns in direct immunofluorescence images Autonomous Systems 2015 - Proceedings of the 8th GI Conference, Fortschritt-Berichte VDI pp 61–69.
- Vorobyev A, Ludwig RJ, Schmidt E. Review Clinical features and diagnosis of epidermolysis bullosa acquisita. Expert Review of Clinical Immunology 2017;13(2):157-169
- Meijer JM, Atefi I, Diercks GFH, Vorobyev A, Zuiderveen J, Meijer HJ, Pas HH, Zillikens D, Schmidt E, Jonkman MF. Optimal technical procedures for serration pattern analysis in direct immunofluorescence microscopy. Protocol for differentiating pemphigoid diseases on skin biopsy. under review
- Meijer JM, Atefi I, Diercks GFH, Vorobyev A, Zuiderveen J, Meijer HJ, Pas HH, Zillikens D, Schmidt E, Jonkman MF. Serration pattern analysis for differentiating epidermolysis bullosa acquisita from other pemphigoid diseases. Journal of the American Academy of Dermatology 2018;78(4):754-759.e6
- Meijer JM, Diercks GFH, de Lang EWG, Pas HH, Jonkman MF. Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid. JAMA Dermatology 2019;155(2):158–165.
- Shi C, Meijer JM, Guo J, Azzopardi G, Diercks GFH, Schmidt E, Zillikens D, Jonkman MF, Petkov N. Detection of u-serrated patterns in direct immunofluorescence images of autoimmune bullous diseases by inhibition-augmented COSFIRE filters. International Journal of Medical Informatics 2019:122:27-36
- Rashid H, Meijer JM, Diercks GFH, Sieben NE, Bolling MC, Pas HH, Horvath B. Assessment of Diagnostic Strategy for Mucous Membrane Pemphigoid. JAMA Dermatology. Published online April 28, 2021. doi:10.1001/jamadermatol.2021.1036
- Shi C, Meijer JM, Azzopardi G, Diercks GFH, Guo J, Petkov N. Use of convolutional neural networks for the detection of u-serrated patterns in direct immunofluorescence images to facilitate the diagnosis of epidermolysis bullosa acquisita. American Journal of Pathology 2021 accepted for publication
- Bernard P, Borradori L. Vesiculobullous diseases. pemphigoid group. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia: Elsevier Saunders; 2012:475-490
- Schmidt E, Groves R. Immunobullous diseases. In: Griffiths C, Barker J, Bleiker T, Chalmers R, Creamer D, eds. Rook’s textbook of dermatology. 9th ed. Wiley-Blackwell; 2016:50.01-50-56
- Jonkman MF (ed). Autoimmune Bullous Diseases. Text and Review. Springer International Publishing, 2016.
Update May 2021