The place of laser fluorescence spectroscopy, doppler flowmetry and ultrasound in the diagnosis and assessment of treatment efficacy for plaque scleroderma

Abstract

According to modern ideas, a reasonable choice of an effective method of treating plaque scleroderma is based on the diagnosis of the pathological process prevailing in the tissues (inflammation-sclerosis). Therefore, an urgent problem of a personalized approach to dermatosis therapy is the possibility of an objective assessment of the prevailing process using non-invasive diagnostic methods. The article presents a clinical case of widespread plaque scleroderma in a 66-year-old patient, demonstrating the possibility of using laser fluorescence spectroscopy and laser Doppler flowmetry to determine the degree of activity of the focus and determine the leading pathological process.

We selected three pathological skin foci localized in the abdomen and characterizing three clinical stages of the disease (inflammation, induration, sclerosis). The analysis of fluorescence and laser Doppler flowmetry data showed that in areas clinically defined as inflammation, there is an increase in the average values of the indices of tissue content of porphyrins, lipofuscin and microcirculation index compared with intact skin, while the intensity of collagen fluorescence does not differ significantly. In the induration zone, along with an increase in the fluorescence indices of lipofuscin and porphyrins, there is an increase in the average values of collagen fluorescence indices at effective registration waves. The data obtained by us indicate an active inflammatory process in these foci and the process of fibrosis in the induration zone. In the sclerosis zone, there is an increase in the average values of collagen fluorescence indices compared with intact skin, and the fluorescence of optical markers of inflammation (lipofuscin and porphyrins) do not differ significantly in comparison with the control intact skin. When analyzing the fluorescence spectra and laser Doppler flowmetry data after treatment, we found that in the zones of induration and inflammation, the average values of the fluorescence indices of porphyrins, lipofuscin, collagen and microcirculation index are reduced relative to the initial values (before treatment), but remain higher in comparison with intact skin. The data obtained may indicate that active inflammation in these foci persists at the time of the study. In the study of the focus of sclerosis, the obtained autofluorescence and microcirculation data in dynamics do not differ significantly from the initial values. The data for laser Doppler flowmetry and laser fluorescence spectroscopy are consistent with ultrasound examination of the skin.

In our study, the potential possibility of using laser fluorescence spectroscopy and laser Doppler flowmetry methods to establish the degree of activity of the focus, determine the leading pathological process, as well as to evaluate the effectiveness of therapy was demonstrated for the first time.

Keywords

plaque scleroderma / non-invasive diagnostics / autofluorescence / laser fluorescence spectroscopy / ultrasound diagnostics / effectiveness of treatment

References

[1] Butova YS, Skripkina YK, Ivanova OL. Dermatovenerology. National leadership. Short edition. Moscow: GEOTAR-Media; 2013. Р. 505–513. (In Russ).

[2] Бутова Ю.С., Скрипкина Ю.К., Иванова О.Л. Дерматовенерология. Национальное руководство. Краткое издание. Москва: ГЭОТАР-Медиа, 2013. С. 505–513.

[3] Gilbane AJ, Denton CP, Holmes AM. Scleroderma pathogenesis: a pivotal role for fibroblasts as effector cells. Arthritis Res Ther. 2013;15(3):215. doi: 10.1186/ar4230

[4] Gilbane A.J., Denton C.P., Holmes A.M. Scleroderma pathogenesis: a pivotal role for fibroblasts as effector cells // Arthritis Res Ther. 2013. Vol. 15, N 3. Р. 215. doi: 10.1186/ar4230

[5] Clinical guidelines for localized scleroderma. The Russian Society of Dermatovenerologists and Cosmetologists and the Association of Rheumatologists of Russia; 2020. Available from: https://www.rodv.ru/klinicheskie-rekomendacii/. Accessed: 21.08.2022.

[6] Клинические рекомендации по локализованной склеродермии. Российское общество дерматовенерологов и косметологов, Ассоциация ревматологов России, 2020. Режим доступа: https://www.rodv.ru/klinicheskie-rekomendacii/. Дата обращения: 21.08.2022.

[7] Peterson LS, Nelson AM, Su WP, et al. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960–1993. J Rheumatol. 1997;24(1):73–80.

[8] Peterson L.S., Nelson A.M., Su W.P., et al. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960–1993 // J Rheumatol. 1997. Vol. 24, N 1. Р. 73–80.

[9] Murray KJ, Laxer RM. Scleroderma in children and adolescents. Rheum Dis Clin North Am. 2002;28(3):603–624. doi: 10.1016/s0889-857x(02)00010-8

[10] Murray K.J., Laxer R.M. Scleroderma in children and adolescents // Rheum Dis Clin North Am. 2002. Vol. 28, N 3. Р. 603–624. doi: 10.1016/s0889-857x(02)00010-8

[11] Leitenberger JJ, Cayce RL, Haley RW, et al. Distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases. Arch Dermatol. 2009;145(5):545–550. doi: 10.1001/archdermatol.2009.79

[12] Leitenberger J.J., Cayce R.L., Haley R.W., et al. Distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases // Arch Dermatol. 2009. Vol. 145, N 5. Р. 545–550. doi: 10.1001/archdermatol.2009.79

[13] Kubanova AA, Kubanov AA, Melekhina LE, Bogdanova EV. Analysis of the state of morbidity of skin and subcutaneous tissue diseases in the Russian Federation for the period 2003–2016. Bulletin Dermatol Venereol. 2017;(6):22–33. (In Russ). doi: 10.25208/0042-4609-2017-93-6-22-33

[14] Кубанова А.А., Кубанов А.А., Мелехина Л.Е., Богданова Е.В. Анализ состояния заболеваемости болезнями кожи и подкожной клетчатки в Российской Федерации за период 2003–2016 гг. // Вестник дерматологии и венерологии. 2017. № 6. С. 22–33. doi: 10.25208/0042-4609-2017-93-6-22-33

[15] Fett N, Werth VP. Update on morphea: part I. Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol. 2011;64(2):217–230. doi: 10.1016/j.jaad.2010.05.045

[16] Fett N., Werth V.P. Update on morphea: part I. Epidemiology, clinical presentation, and pathogenesis // J Am Acad Dermatol. 2011. Vol. 64, N 2. Р. 217–230. doi: 10.1016/j.jaad.2010.05.045

[17] Knobler R, Moinzadeh P, Hunzelmann N, et al. European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes. J Eur Acad Dermatol Venereol. 2017;31(9):1401–1424. doi: 10.1111/jdv.14458

[18] Knobler R., Moinzadeh P., Hunzelmann N., et al. European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes // J Eur Acad Dermatol Venereol. 2017. Vol. 31, N 9. Р. 1401–1424. doi: 10.1111/jdv.14458

[19] Kreuter A, Krieg T, Worm M, et al. German guidelines for the diagnosis and therapy of localized scleroderma. J Dtsch Dermatol Ges. 2016;14(2):199–216. doi: 10.1111/ddg.12724

[20] Kreuter A., Krieg T., Worm M., et al. German guidelines for the diagnosis and therapy of localized scleroderma // J Dtsch Dermatol Ges. 2016. Vol. 14, N 2. Р. 199–216. doi: 10.1111/ddg.12724

[21] Mertens JS, Seyger MM, Thurlings RM, et al. Morphea and eosinophilic fasciitis: an update. Am J Clin Dermatol. 2017;18(4): 491–512. doi: 10.1007/s40257-017-0269-x

[22] Mertens J.S., Seyger M.M., Thurlings R.M., et al. Morphea and eosinophilic fasciitis: an update // Am J Clin Dermatol. 2017. Vol. 18, N 4. Р. 491–512. doi: 10.1007/s40257-017-0269-x

[23] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009;360(19):1989–2003. doi: 10.1056/NEJMra0806188

[24] Gabrielli A., Avvedimento E.V., Krieg T. Scleroderma // N Engl J Med. 2009. Vol. 360, N 19. Р. 1989–2003. doi: 10.1056/NEJMra0806188

[25] George R, George A, Kumar TS. Update on management of morphea (localized scleroderma) in children. Indian Dermatol Online J. 2020;11(2):135–145. doi: 10.4103/idoj.IDOJ_284_19

[26] George R., George A., Kumar T.S. Update on management of morphea (localized scleroderma) in children // Indian Dermatol Online J. 2020. Vol. 11, N 2. Р. 135–145. doi: 10.4103/idoj.IDOJ_284_19

[27] Bendeck SE, Jacobe HT. Ultrasound as an outcome measure to assess disease activity in disorders of skin thickening: an example of the use of radiologic techniques to assess skin disease. Dermatol Ther. 2007;20(2):86–92. doi: 10.1111/j.1529-8019.2007.00116.x

[28] Bendeck S.E., Jacobe H.T. Ultrasound as an outcome measure to assess disease activity in disorders of skin thickening: an example of the use of radiologic techniques to assess skin disease // Dermatol Ther. 2007. Vol. 20, N 2. Р. 86–92. doi: 10.1111/j.1529-8019.2007.00116.x

[29] Li SC, Liebling MS, Haines KA. Ultrasonography is a sensitive tool for monitoring localized scleroderma. Rheumatology (Oxford). 2007;46(8):1316–1319. doi: 10.1093/rheumatology/kem120

[30] Li S.C., Liebling M.S., Haines K.A. Ultrasonography is a sensitive tool for monitoring localized scleroderma // Rheumatology (Oxford). 2007. Vol. 46, N 8. Р. 1316–1319. doi: 10.1093/rheumatology/kem120

[31] Hoffmann K, Gerbaulet U, el-Gammal S, Altmeyer P. 20-MHz B-mode ultrasound in monitoring the course of localized scleroderma (morphea). Acta Derm Venereol Suppl (Stockh). 1991;164:3–16.

[32] Hoffmann K., Gerbaulet U., El-Gammal S., Altmeyer P. 20-MHz B-mode ultrasound in monitoring the course of localized scleroderma (morphea) // Acta Derm Venereol Suppl (Stockh). 1991. Vol. 164. Р. 3–16.

[33] Moiseev AA, Utts SR. Modern methods of diagnosis of limited scleroderma (review). Saratov Sci Med J. 2016;12(3):481–484. (In Russ).

[34] Моисеев А.А., Утц С.Р. Современные методы диагностики ограниченной склеродермии (обзор) // Саратовский научно-медицинский журнал 2016. Т. 12, № 3. С. 481–484.

[35] Weibel L, Howell KJ, Visentin MT, et al. Laser Doppler flowmetry for assessing localized scleroderma in children. Arthritis Rheum. 2007;56(10):3489–3495. doi: 10.1002/art.22920

[36] Weibel L., Howell K.J., Visentin M.T., et al. Laser Doppler flowmetry for assessing localized scleroderma in children // Arthritis Rheum. 2007. Vol. 56, N 10. Р. 3489–3495. doi: 10.1002/art.22920

[37] Serup J, Kristensen JK. Blood flow of morphoea plaques as measured by laser-Doppler flowmetry. Arch Dermatol Res. 1984;276(5):322–325. doi: 10.1007/BF00404625

[38] Serup J., Kristensen J.K. Blood flow of morphoea plaques as measured by laser-Doppler flowmetry // Arch Dermatol Res. 1984. Vol. 276, N 5. Р. 322–325. doi: 10.1007/BF00404625

[39] Kalis B, De Rigal J, Léonard F, et al. In vivo study of scleroderma by non-invasive techniques. Br J Dermatol. 1990;122(6):785–791. doi: 10.1111/j.1365-2133.1990.tb06267.x

[40] Kalis B., De Rigal J., Léonard F., et al. In vivo study of scleroderma by non-invasive techniques // Br J Dermatol. 1990. Vol. 122, N 6. Р. 785–791. doi: 10.1111/j.1365-2133.1990.tb06267.x

[41] Chursinova YV, Kulikov DA, Rogatkin DA, et al. Laser fluorescence spectroscopy and optical tissue oximetry in the diagnosis of skin fibrosis. Biomedical Photonics. 2019;8(1):38–45. (In Russ). doi: 10.24931/2413-9432-2019-8-1-38-45

[42] Чурсинова Ю.В., Куликов Д.А., Рогаткин Д.А., и др. Лазерная флуоресцентная спектроскопия и оптическая тканевая оксиметрия в диагностике фиброза кожи // Biomedical Photonics. 2019. Т. 8, № 1. С. 38–45. doi: 10.24931/2413-9432-2019-8-1-38-45

[43] Helmbold P, Fiedler E, Fischer M, Marsch WC. Hyperplasia of dermal microvascular pericytes in scleroderma. J Cutan Pathol. 2004;31(6):431–440. doi: 10.1111/j.0303-6987.2004.00203.x

[44] Helmbold P., Fiedler E., Fischer M., Marsch W.C. Hyperplasia of dermal microvascular pericytes in scleroderma // J Cutan Pathol. 2004. Vol. 31, N 6. Р. 431–440. doi: 10.1111/j.0303-6987.2004.00203.x

[45] Petritskaya EN, Kulikov DA, Rogatkin DA, et al. Use of fluorescence spectroscopy for diagnosis of hypoxia and inflammatory processes in tissue. J Optical Technol. 2015;82(12):810–814. doi: 10.1364/JOT.82.000810

[46] Petritskaya E.N., Kulikov D.A., Rogatkin D.A., et al. Use of fluorescence spectroscopy for diagnosis of hypoxia and inflammatory processes in tissue // J Optical Technol. 2015. Vol. 82, N 12. Р. 810–814. doi: 10.1364/JOT.82.000810

[47] Kaznacheeva EV, Khinku EF, Makmatov-Rys MB, et al. Lipofuscin as a marker of aging, oxidative stress and proteolysis disorders. Bulletin Postgraduate Med Education. 2020;(3):19–23. (In Russ).

[48] Казначеева Е.В., Хынку Е.Ф., Макматов-Рысь М.Б., и др. Липофусцин как маркер старения, оксидативного стресса и нарушений протеолиза // Вестник последипломного медицинского образования. 2020. № 3. С. 19–23.

[49] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009;360(19):1989–2003. doi: 10.1056/NEJMra0806188

[50] Gabrielli A., Avvedimento E.V., Krieg T. Scleroderma // N Engl J Med. 2009. Vol. 360, N 19. Р. 1989–2003. doi: 10.1056/NEJMra0806188

Funding

ГБУЗ МО МОНИКИ им. М.Ф. ВладимирскогоMoscow Regional Research and Clinical Institute(НИР 2)

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