Abstract
Morphea is an inflammatory fibrosing disease, initiated by vascular injury resulting in increased collagen formation and decreased collagen degradation. This study was designed to evaluate the role of angiogenic vascular endothelial growth factor (VEGF) in the vascular changes which are dermoscopically evident in morphea lesions, compared with that in non-lesional skin, by assessing its expression immunohistochemically on tissue blood vessels. Twenty patients with morphea were subjected to clinical and dermoscopic examinations. Two skin biopsies from lesional and non-lesional skin were obtained and stained with hematoxylin and eosin (H&E) and immunohistochemically with VEGF. Dermoscopic examination showed linear blood vessels in 90% of the lesions. No significant difference in the number of VEGF-stained and unstained blood vessels, was observed between the lesional and non-lesional skin (p = 0.475 and 0.191, respectively). A weak inverse correlation was found between the total number of blood vessels positive for VEGF and the disease duration, (r = − 0.48; p = 0.032). Significant differences were found between different stages of morphea and total number of blood vessels negative for VEGF, (p = 0.017). In conclusion, VEGF immunostaining, which represents the newly formed blood vessels, showed no difference between lesional and non-lesional skin in patients with morphea. Thus, the dermoscopically observable blood vessels in lesions compared with non-lesional skin are not due to angiogenesis, but rather due to the thinning and atrophy of the overlying epidermis in morphea cases, rendering the blood vessels more obvious.
Similar content being viewed by others
References
Abbas L, Joseph A, Kunzler E, Jacobe HT (2021) Morphea: progress to date and the road ahead. Ann Transl Med 9(5):437
Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H (2009) The role of vascular endothelial growth factor in wound healing. J Surg Res 153(2):347–358
Bhat YJ, Akhtar S, Hassan I (2019) Dermoscopy of Morphea. Indian Dermatol Online J 10(1):92–93.
Bosseila M, Sayed Sayed K, El-Din Sayed SS, Abd El Monaem NA (2015) Evaluation of angiogenesis in early mycosis fungoides patients: dermoscopic and immunohistochemical study. Dermatology. 231(1):82–6.
Campione E, Paterno EJ, Diluvio L, Orlandi A, Bianchi L, Chimenti S (2009) Localized morphea treated with imiquimod 5% and dermoscopic assessment of effectiveness. J Dermatolog Treat 20(1):10–13
Cantatore FP, Maruotti N, Corrado A, Ribatti D (2017) Angiogenesis dysregulation in the pathogenesis of systemic sclerosis. Biomed Res Int 2017:5345673
Careta MF, Romiti R (2015) Localized scleroderma: clinical spectrum and therapeutic update. An Br Dermatol 90(1):62–73.
Cipriani P, Marrelli A, Liakouli V, Di Benedetto P, Giacomelli R (2011) Cellular players in angiogenesis during the course of systemic sclerosis. Autoimmun Rev 10(10):641–646
Distler O, Distler JH, Scheid A, Acker T, Hirth A, Rethage J et al (2004) Uncontrolled expression of vascular endothelial growth factor and its receptors leads to insufficient skin angiogenesis in patients with systemic sclerosis. Circ Res 95(1):109–116
El-Zawahry MB, Abdel El-Hameed El-Cheweikh HM, Abd-El-Rahman Ramadan S, Ahmed Bassiouny D, Mohamed Fawzy M (2007) Ultrasound biomicroscopy in the diagnosis of skin diseases. Eur J Dermatol 17(6):469–475
Errichetti E, Lallas A, Apalla Z, Di Stefani A, Stinco G (2017) Dermoscopy of morphea and cutaneous lichen sclerosus: clinicopathological correlation study and comparative analysis. Dermatology 233(6):462–470
Florez-Pollack S, Kunzler E, Jacobe HT (2018) Morphea: current concepts. Clin Dermatol 36(4):475–486
Helmbold P, Fiedler E, Fischer M, Marsch W (2004) Hyperplasia of dermal microvascular pericytes in scleroderma. J Cutan Pathol 31(6):431–440
Lallas A, Kyrgidis A, Tzellos TG, Apalla Z, Karakyriou E, Karatolias A et al (2012) Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. Br J Dermatol 166(6):1198–1205
Low A.H.L., Ng S, Berrocal V, Brennan B, Chan G, Ng S, Khanna D. Evaluation of Scleroderma Clinical Trials Consortium training recommendations on modified Rodnan skin score assessment in scleroderma. Int J Rheum Dis. 2019 Jun; 22(6): 1036–1040.
Mackiewicz Z, Sukura A, Povilenaite D, Ceponis A, Virtanen I, Hukkanen M et al (2002) Increased but imbalanced expression of VEGF and its receptors has no positive effect on angiogenesis in systemic sclerosis skin. Clin Exp Rheumatol 20(5):641–646
Manetti M, Guiducci S, Ibba-Manneschi L, Matucci-Cerinic M (2010) Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus vasculogenesis. J Cell Mol Med 14(6A):1241–1254
Mertens JS, Seyger MMB, Thurlings RM, Radstake T, de Jong E (2017) Morphea and Eosinophilic fasciitis: an update. Am J Clin Dermatol 18(4):491–512
Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown J et al (2018) Mechanisms of VEGF (vascular endothelial growth factor) inhibitor-associated hypertension and vascular disease. Hypertension 71(2):e1–e8
Sartori-Valinotti JC, Tollefson MM, Reed AM (2013) Updates on morphea: role of vascular injury and advances in treatment. Autoimmune Dis 2013:467808
Shim WH, Jwa SW, Song M, Kim HS, Ko HC, Kim MB et al (2012) Diagnostic usefulness of dermatoscopy in differentiating lichen sclerous et atrophicus from morphea. J Am Acad Dermatol 66(4):690–691
Zalaudek I, Kreusch J, Giacomel J, Ferrara G, Catricala C, Argenziano G (2010) How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. Melanocytic skin tumors. J Am Acad Dermatol 63(3):361–374; quiz 75–6.
Funding
None.
Author information
Authors and Affiliations
Contributions
MB: contributed to the research idea, dermoscopic evaluation of the patients, data analysis, writing of the first draft of the manuscript, manuscript revision; SS: performed the histopathological examination of all patients; AO: collected the patients` information, did the dermoscopic examination and collected the patients` biopsies; MAS: contributed to the research idea, revised the manuscript and submitted the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
None declared.
Ethical approval
This work was approved by the Dermatology Department of Cairo University.
Consent to participate
All patients provided informed consent to participate in this study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bosseila, M., Okail, A., Sayed, S. et al. Comparison of vascular endothelial growth factor expression between lesional and non-lesional skin in patients with morphea: a dermoscopy-guided immunohistochemical study. Arch Dermatol Res 315, 61–66 (2023). https://doi.org/10.1007/s00403-021-02315-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-021-02315-x