Significant difference between three observers in the assessment of intraepidermal nerve fiber density in skin biopsyReport as inadecuate

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BMC Neurology

, 9:13

First Online: 31 March 2009Received: 08 July 2008Accepted: 31 March 2009


BackgroundThe determination of Intraepidermal Nerve Fiber Density IENFD in skin biopsy is a useful method for the evaluation of different types of peripheral neuropathies. To allow a reliable use of the method it is necessary to determine interobserver reliability. Previous studies dealing with this topic used limited suitable statistical methods.

MethodsIn the present study three observers determined the IENFD and estimated the staining quality of the basement membrane for an adequate quantity of 120 skin biopsies stained with indirect immunofluorescence technique from 68 patients. More adequate statistical methods like intraclass correlation coefficient and Bland Altman Plot were chosen to estimate interobserver reliability.

ResultsWe found an unexpected significant difference in IENFD between the observers p < 0.05 and so the results of this study are not in line with the high interobserver reliability reported before intraclass correlation coefficient: 0.73. The Bland Altmann Plot showed a variance growing with rising mean. The difference in IENFD between the observers and the resulting low interobserver reliability is likely caused by different interpretations of the standard counting rules. There was no significant difference in IENFD between observers for biopsies with a well-defined basement membrane. Thus skin biopsies with an inexactly defined basement membrane should not be used diagnostically for the determination of IENFD.

ConclusionThese results emphasise that standardisation of the method is extremely important and at least two observers should analyse skin biopsies with critical IENFD near the cut-off values.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2377-9-13 contains supplementary material, which is available to authorized users.

Sigrid Wöpking, Andrea Scherens contributed equally to this work.

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Author: Sigrid Wöpking - Andrea Scherens - Ida S Haußleiter - Helmut Richter - Julia Schüning - Sabrina Klauenberg - Christoph 


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