Autofluorescence Imaging of the Skin Is an Objective Non-Invasive Technique for Diagnosing Pseudoxanthoma Elasticum

Abstract

Pseudoxanthoma elasticum (PXE) is a rare multisystemic autosomal recessive connective tissue disease. In most cases, skin manifestations of PXE are the first to develop, followed later by severe ocular and cardiovascular complications. In our present study, in addition to dermoscopy, we introduced novel techniques, autofluorescence (AF) and diffuse reflectance (DR) imaging for the assessment of affected skin sites of five PXE patients. PXE-affected skin areas in most skin sites showed a previously observed pattern upon dermoscopic examination. With the novel imaging, PXE-affected skin lesions displayed high AF intensity. During our measurements, significantly higher mean, minimum and maximum AF intensity values were found in areas of PXE-affected skin when compared to uninvolved skin. Conversely, images acquired with the use of 660 and 940 nm illumination showed no mentionable difference. Our results demonstrate that AF imaging may be used in the in vivo diagnostics and quantification of the severity of the skin lesions of PXE patients. In addition, it is a safe, fast and cost-effective diagnostic method. AF imaging may be also used to objectively monitor the efficacy of the possible novel therapeutic approaches of PXE in the future.

Keywords: LED; autofluorescence imaging; calcification; dermoscopy; diagnosis; diffuse reflectance imaging; pseudoxanthoma elasticum; quantitative analysis.

Figure 1

Clinical photographs that display the typical cutaneous manifestations of the patients with pseudoxanthoma elasticum. (a) Patient 1, large coalescent plaques on the wrist (b) Patient 2, 1–2 mm yellowish papules on the right side of the neck (c) Patient 3, redundant, loose skin in the axilla and 2–5 mm papules on the axilla (d) Patient 4, 2–6 mm papules on the right and dorsal side of the neck (e) Patient 5, right antecubital fossa, yellow-white flat plaques.

Figure 2

Histopathological characteristics of skin biopsies of the pseudoxanthoma elasticum patients (Pt) with hematoxylin and eosin (H&E), von Kossa (VK) staining for calcium deposits, Weigert’s elastic (WE) staining for elastin and van Gieson (VG) staining for collagen. Scale bars display 100 μm.

Figure 3

Representative dermoscopic images of the skin lesions of the patients with pseudoxanthoma elasticum. (a) Patient 1, linear pattern on the cubital fossa. (b) Patient 2, dots on the neck. (c) Patient 3, narrow mesh network on the axilla. (d) Patient 4, broad mesh network on the neck. (e) Patient 5, plaques of confluent dots and linear patterns in the antecubital fossa. Black markers do not point to areas of interest, they are used for image alignment (area: 0.125 cm²).

Figure 4

Representative autofluorescence (AF), diffuse reflectance (DR) and dermoscopy (DS) images of the affected skin sites of the pseudoxanthoma elasticum patients. (a) AF image of the axilla of Patient (Pt) 1. (b) AF, DR and DS images of the antecubital fossa of Pt 1, showing PXE-specific morphologic structures. (c) AF image of the axilla of Pt 2. (d) AF, DR and DS images of the inguinal region of Pt 2. AF image reveals a well-visible extensive area with high AF signal. DR images show barely noticeable pattern. DS image shows no typical pattern. (e) AF image of the antecubital fossa of Pt 3. (f) AF, DR and DS images of the neck of Pt 3, showing PXE-specific morphologic structures. (g) AF image from popliteal fossa of Pt 4. (h) AF, DR and DS images from wrist of Pt 4. AF image gives high-contrast signal. DR images are less informative. (i) AF image of the inguinal region of Pt 5. (j) AF, DR and DS images of the axilla of Pt 5, displaying PXE-specific morphologic structures. (k) AF images of Pt 5, uninvolved normal skin. (l) AF, DR and DS images of uninvolved normal skin, upper arm of Pt 5. The size of the images is 2 × 2 cm². Black markers do not point to areas of interest, they are used for image alignment (area: 0.125 cm²).

Figure 5

Regions of interest (ROI) selection and results of quantitative analyses of autofluorescence (AF) and diffuse reflectance (DR) images of the skin of the pseudoxanthoma elasticum (PXE) patients. (a) Marked PXE-affected and uninvolved skin areas as ROI. Patient (Pt) 1, neck; Pt 2, antecubital fossa; Pt 3, axilla; Pt 4, wrist; Pt 5, antecubital fossa. (b) In the AF images, the investigated parameters were significantly increased in PXE-affected skin compared to uninvolved skin. Analyzing DR images, no significant differences were found between PXE-affected and healthy skin. * p < 0.05. A.U., arbitrary unit.