Figures
Abstract
Background
Dilated and tortuous vessels within elongated dermal papillae represent a histopathological clue of psoriasis. However, the number of dilated capillaries (capillary density) in psoriasis remains undefined as the results from the available studies differ significantly.
Objectives
To evaluate the capillary density in psoriasis using dermoscopy and horizontal histopathological sections (HHS), two techniques that share the horizontal view of the skin, and to compare the results with the existing data.
Methods
Twenty adult patients with stable plaque psoriasis were enrolled and, in each patient, a target area of the examined plaque, previously engraved by gently rotating a 5-mm biopsy punch device, underwent dermoscopy and biopsy for HHS. In all examined fields, capillary density was evaluated in a centered 4-mm diameter area, counting the number of red dots at dermoscopy and of dermal papillae at HHS.
Results
A total of 20 target lesions located on the trunk, arms and tights were evaluated. The mean capillary density resulting from dermoscopy was 43.02±6.60/mm 2 whereas that from HHS was 50.30±9.05/mm 2. These data showed a statistically significant difference (p = 0.006), with a strong correlation at Pearson’s test (r = 0.88).
Conclusions
Our results when compared with those from the existing literature showed some differences. The peculiarity of our work is represented by the precise measurement and correlation of the capillary density using two different methods, as the preliminary skin engraving allowed a perfect match between the area undergoing dermoscopy and that of skin sampling for HHS. Compared to dermoscopy in which deep-located vessels might have gone undetected, HHS seems to reflect more precisely and reliably the real capillary density showing an average of 50 capillaries/mm 2 that in a common 5x5 cm psoriatic patch corresponds to an average of 125.000 capillaries. These results highlight the extraordinary potential of psoriatic skin to develop such a complex and intricate vascular network.
Citation: Micali G, Verzì AE, Broggi G, Caltabiano R, Musumeci ML, Lacarrubba F (2021) Evaluation of capillary density in psoriasis: An intrapatient study and literature review. PLoS ONE 16(3): e0247835. https://doi.org/10.1371/journal.pone.0247835
Editor: Beatrice Nardone, Northwestern University Feinberg School of Medicine Galter Health Sciences Library, UNITED STATES
Received: November 14, 2020; Accepted: February 12, 2021; Published: March 10, 2021
Copyright: © 2021 Micali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and Supporting Information files.
Funding: The authors received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Psoriasis is a common skin disease whose complex pathogenetic mechanisms including vascular remodeling have recently been demonstrated. Dilated and tortuous vessels within elongated dermal papillae represent a histopathological clue also evident by dermoscopy, a non-invasive technique that magnifies (X10) the skin surface, as uniformly distributed “red dots” [1, 2]. A recent study using horizontal histopathological sections (HHS) on psoriatic skin confirmed the presence of roundish dermal papillae at the dermo-epidermal junction each centered by ectatic capillaries [3]. However, the number of dilated capillaries (i.e. capillary density) in psoriasis remains undefined as the results from the available studies differ significantly [4–13].
The objectives of this study were to evaluate the capillary density in psoriasis using HHS and to compare the results with those obtained using dermoscopy, also sharing the horizontal view of the skin, and with the existing data.
Materials and methods
Twenty adult patients with stable plaque psoriasis (9 males, 11 females; median age: 46.3 years) were enrolled in the study after obtaining informed consent. Exclusion criteria were treatments with topical or systemic anti-psoriatic drugs in the last 2 or 4 weeks, respectively, as well as phototherapy/sun exposure in the previous 4 weeks, pregnancy, smoking and/or alcohol assumption, presence of microangiopathic diseases including diabetes and connective vascular diseases. Hyperkeratotic plaques were excluded as scales may hamper the dermoscopic visualization of the vascular pattern. Fifteen minutes before and during the examinations, patients stood in supine position in a temperature/humidity-controlled room. In each patient, a target area of the examined plaque previously engraved by gently rotating a 5-mm biopsy punch device, underwent dermoscopy using a x10 magnification polarized instrument (Dermlite/3GenTM) connected to a digital camera, then local anesthesia with 1% mepivacaine solution, and finally skin sampling for HHS (Fig 1A and 1B). After paraffin embedding, consecutive 5-μm thick sections from the stratum corneum down to the superficial dermis were obtained for HHS and stained with standard Hematoxylin-Eosin. For evaluation accuracy, in all examined fields, capillary density was evaluated in a centered 4-mm diameter area, counting the number of red dots at dermoscopy (Fig 1C) and of dermal papillae at the dermo-epidermal junction at HHS (Fig 1D) by 2 different operators (AEV and FL, respectively). For each biopsy, the histological section containing the maximum count of dermal papillae was considered. Pearson’s test was performed to evaluate the correlation between the 2 methods. The study was approved by the local human research board (Catania 1). Written consent was obtained from patients and data were analyzed anonymously.
Stable psoriatic plaque of the lower leg before (a) and after engraving a target area by gently rotating a 5-mm biopsy punch device (b). Dermoscopy (x10) (c) and HHS (H&E stain: x100) (d) of the target area: the capillary density was evaluated in both cases in a centered 4-mm diameter area (yellow circle) by counting the number of red dots and of dermal papillae, respectively.
Results
A total of 20 target lesions located on the trunk (10 cases), arms (5 cases) and thighs (5 cases) were evaluated.
The mean capillary density resulting from HHS was 50.30±9.05/mm2, whereas that from dermoscopy was 43.02±6.60/mm2. These results showed a strong correlation at Pearson’s test (r = 0.88).
Discussion
In conjunction with epidermal hyperplasia, papillomatosis and inflammatory infiltrate, the expansion of the superficial dermal microvasculature represents one of the main histopathological changes in psoriatic skin. It consists of the presence of dilated and tortuous vessels within elongated dermal papillae, describing multiple loops in their trajectory [14]. This microvascular aspect has been evaluated by different techniques [Table 1] including dermoscopy, videocapillaroscopy (or capillaroscopy), fluorescence angiography, reflectance confocal microscopy (RCM) and histopathology [15].
The review of the existing literature on the different techniques to evaluate capillary density in psoriasis [4–13] has shown several critical issues [Table 2]. All studies differed for multiple factors including study design, methodology, and heterogeneity of results according to the instrumentation used. Also, many studies dealt with a limited sample of patients [5, 7, 11, 12]. As regards study design, the main differences consisted in non standardized exclusion criteria, with studies excluding subjects with microangiopathic disease such as diabetes and connective vascular disorders [7–10], and others not specifying any [4–6, 11–13]. Also, the site of the target plaque was variable (scalp, elbow, forearm, etc.) or unspecified [6, 7, 13]. Most studies evaluated untreated plaques, and wash out from previous treatments were quite variable [6–8, 10–12]. Methodology also varied as in some studies the instrumental evaluation was preceded by removal of scales using a lancet, a tape stripping or a keratolytic agent [4, 8, 10–12] whereas, in others, hyperkeratotic plaques were excluded a priori [5]. Investigational setting in most of the cases was not standardized, with few studies specifying room temperature and patient position during evaluation [4, 6–8, 10]. Also, terminology of the evaluated parameters varied from number of “capillaries” to “capillary loops”, “microvessels”, “red dots” or “dermal papillae”. The results were also quite heterogeneous as in 4 studies using videocapillaroscopy at different magnifications to count the number of capillary loops, the results ranged from a mean of ~22/mm2 to a mean of ~53/mm2 [4, 6–8, 10]. Another videocapillaroscopy study estimated the number of capillaries per “field”, but the measurement unit of the observation area was not specified [9]. As regards capillary density evaluation by RCM, considering that each dermal papilla is centred by a capillary loop, the number of capillaries likely corresponds to the number of dermal papillae. Existing studies show contrasting results, with a density ranging from a mean of 8.12/mm2 to a mean of ~216/mm2 [5, 12, 13]. In another study that compared RCM (8 lesions) with HHS (5 lesions), the number of dermal papillae ranged from ~294/mm2 to~100/mm2, respectively [11]. In the same study, dermoscopy showed “red dots” density of 36.7/mm2 [11].
Peculiarities of our work are represented by a rigorous standardization of the inclusion/exclusion criteria and methods and by the use of 2 different techniques able to provide a horizontal view of the skin, with one of them being histopathology, which represents the gold standard for skin structure evaluation. Of note, the preliminary skin engraving allowed a perfect match between the area undergoing dermoscopy and that of skin sampling for HHS. In our study, HHS showed a mean density of ~50/mm2 dermal papillae and the results obtained by dermoscopy were similar (~43/mm2). Pearson’s test demonstrated a strong correlation between the two techniques. Although capillary density resulting from dermoscopy was slightly lower compared to HHS likely due to deep-located vessels that might have gone undetected, dermoscopy, irrespective of the number of capillaries that may be observed, confirmed to be a useful non-invasive technique to evaluate the vascular pattern in psoriasis for diagnostic and research purposes (15).
An average of 50 capillaries/mm2 corresponds, in a common 5x5 cm psoriatic patch, to about 125.000 capillaries. These results confirm the extraordinary potential of psoriatic skin to develop such a complex and intricate vascular network. Whether the capillary density is reactive or rather plays a pathogenetic role needs to be defined. For future studies, a standardization of the patient selection and methodology, independently to the imaging technique used, is advisable.
References
- 1. Micali G, Lacarrubba F, Musumeci ML, Massimino D, Nasca MR. Cutaneous vascular patterns in psoriasis. Int J Dermatol 2010;49(3):249–56. pmid:20465659
- 2. Lacarrubba F, Ardigò M, Di Stefani A, Verzì AE, Micali G. Dermatoscopy and reflectance confocal microscopy correlations in nonmelanocytic disorders. Dermatol Clin 2018;36(4):487–501. pmid:30201157
- 3. Verzì AE, Lacarrubba F, Caltabiano R, Broggi G, Musumeci ML, Micali G. Reflectance confocal microscopy features of plaque psoriasis overlap with horizontal histopathological sections: a case series. Am J Dermatopathol 2019;41(5):355–357. pmid:30640760
- 4. Bull RH, Bates DO, Mortimer PS. Intravital video-capillaroscopy for the study of the microcirculation in psoriasis. Br J Dermatol 1992;126(5):436–45. pmid:1610683
- 5. González S, Rajadhyaksha M, Rubinstein G, Anderson RR. Characterization of psoriasis in vivo by reflectance confocal microscopy. J Med 1999;30(5–6):337–56. pmid:10851567
- 6. De Angelis R, Bugatti L, Del Medico P, Nicolini M, Filosa G. Videocapillaroscopic findings in the microcirculation of the psoriatic plaque. Dermatology 2002;204(3):236–9. pmid:12037454
- 7. Hern S, Stanton AW, Mellor RH, Harland CC, Levick JR, Mortimer PS. In vivo quantification of the structural abnormalities in psoriatic microvessels before and after pulsed dye laser treatment. Br J Dermatol 2005;152(3):505–11. pmid:15787819
- 8. Rosina P, Zamperetti MR, Giovannini A, Girolomoni G. Videocapillaroscopy in the differential diagnosis between psoriasis and seborrheic dermatitis of the scalp. Dermatology 2007;214(1):21–4. pmid:17191043
- 9. Campanati A, Goteri G, Simonetti O, Ganzetti G, Giuliodori K, et al. Angiogenesis in psoriatic skin and its modifications after administration of etanercept: videocapillaroscopic, histological and immunohistochemical evaluation. Int J Immunopathol Pharmacol 2009;22(2):371–7. pmid:19505391
- 10. Rosina P, Giovannini A, Gisondi P, Girolomoni G. Microcirculatory modifications of psoriatic lesions during topical therapy. Skin Res Technol 2009;15(2):135–8. pmid:19622121
- 11. Wolberink EA, van Erp PE, Teussink MM, van de Kerkhof PC, Gerritsen MJ. Cellular features of psoriatic skin: imaging and quantification using in vivo reflectance confocal microscopy. Cytometry B Clin Cytom 2011;80(3):141–9. pmid:21520401
- 12. Wolberink EA, van Erp PE, de Boer-van Huizen RT, van de Kerkhof PC, Gerritsen MJ. Reflectance confocal microscopy: an effective tool for monitoring ultraviolet B phototherapy in psoriasis. Br J Dermatol 2012;167(2):396–403. pmid:22512282
- 13. Hoogedoorn L, Wolberink EA, van de Kerkhof PC, Hendriks JC, Gerritsen MJ, van Erp PE. Noninvasive differentiation between stable and unstable chronic plaque psoriasis using in vivo reflectance confocal microscopy. J Am Acad Dermatol 2015;73(5):870–2. pmid:26475542
- 14. Creamer D, Allen MH, Sousa A, Poston R, Barker JN. Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis. Br J Dermatol 1997;136(6):859–865. pmid:9217817
- 15. Lacarrubba F, Pellacani G, Gurgone S, Verzì AE, Micali G. Advances in non-invasive techniques as aids to the diagnosis and monitoring of therapeutic response in plaque psoriasis: a review. Int J Dermatol 2015;54(6):626–634. pmid:25772034