Hyperpigmentation after sclerotherapy: modern possibilities for prevention and treatment

Sclerotherapy is one of the most popular and most common techniques for the removal of delated reticular veins and telangiectasias on the lower limbs. Despite the vast pooled experience, this procedure can be accompanied by a number of undesirable side effects, of which post-injection hyperpigmentation, which frequency reaches 80%, is the most unpleasant one. The development of postsclerotherapy hyperpigmentation (PSHP) is associated with extravasation and destruction of red blood cells, which results in transformation of haemoglobin into hemosiderin pigment. PSHP is, by definition, a variant of post-traumatic hemosiderin pigmentation. The likelihood of occurrence and persistence of PSHP is determined by a number of hard controllable factors, including the calibre and location of the target veins, the type, concentration and physical form of the sclerosing agent, the sclerotherapy technique, the method and duration of post-procedural compression, patients’ ethnicity, iron metabolism disorders, concomitant use of a number of drugs, a menstrual cycle phase in women, etc. Hyperpigmentation significantly decreases the patients’ quality of life, which determines the need for the prevention and treatment of this undesirable side effect of phlebosclerosing treatment. Recommendations for prevention of PSHP include a detailed history taking aimed at identifying potential risk factors, in the presence of which it is advisable to use various systemic and topical drugs in the post-procedural period in order to prevent the skin hemosiderin deposition, as well as to apply the extended-cycle compression. In the case of PSHP, procedures aimed at the destruction and utilization of hemosiderin, such as Q-Switched laser and IPL therapy, as well as various peeling options intended to speed up the replacement of pigmented skin with normal, can be applied. For the PSHP prevention and treatment, the use of Contractubex containing cepalin onion extract in combination with allantoin and heparin is a matter of interest. Contractubex is a drug originally intended to optimize wound healing and prevent the formation of hypertrophic scars. At the same time, there is ample publications discussing the possible use of this drug for the management of post-traumatic hyperpigmentation due to the combined action of its components. Our clinical experience confirms the effectiveness of Contractubex in the treatment of PSHP, which determines the feasibility of conducting full-fledged clinical trials and accumulating more pooled experience in this area. 

1. Izzo M., Mariani F., Binaghi F., Amitrano M. Postsclerotherapy Hyperpigmentation: Incidence, Clinical Features and Therapy. In: Negus D., Jantet G., Coleridge-Smith P.D. (eds.). Phlebology ’95. London: Springer; 1995, pp. 550–551. https://doi.org/10.1007/978-1-4471-3095-6_255.

2. Munavalli G.S., Weiss R.A. Complications ofsclerotherapy. Semin Cutan Med Surg. 2007;26(1):22–28. https://doi.org/10.1016/j.sder.2006.12.009.

3. Butov Yu.S., Akhtyamov S.N., Zhukova I.K., Vasenova V.Yu. Practical cosmetology. Moscow: MIA; 2013. 400 p. (In Russ.)

4. Akhtyamov S.N., Butov Yu.S. Practical dermatocosmetology. Moscow: Meditsina; 2008. 400 p. (In Russ.)

5. Goldman M.P., Bennett R.G. Treatment of telangiectasia: a review. J Am Acad Dermatol. 1987;17(2 Pt 1):167–182. https://doi.org/ 10.1016/s0190-9622(87)70187-x.

6. Weiss R.A., Weiss M.A. Incidence of side effects in the treatment of telangiectasias by compression sclerotherapy: hypertonic saline vs. polidocanol. J Dermatol Surg Oncol. 1990;16(9):800–804. https://doi.org/10.1111/j.1524-4725.1990.tb01563.x.

7. Georgiev M. Postsclerotherapy hyperpigmentations: a one-year follow-up. J Dermatol Surg Oncol. 1990;16(7):608–610. https://doi.org/10.1111/j.1524-4725.1990.tb00088.x.

8. Georgiev M. Postsclerotherapy hyperpigmentations. Chromated glycerin as a screen for patients at risk (a retrospective study). J Dermatol Surg Oncol. 1993;19(7):649–652. https://doi.org/10.1111/j.1524-4725.1993.tb00405.x.

9. McCoy S., Evans A., Spurrier N. Sclerotherapy forleg telangiectasia – a blinded comparative trial of polidocanol and hypertonic saline. Dermatol Surg. 1999;25(5):381–385. https://doi.org/10.1046/j.1524-4725.1999.08263.x.

10. Goldman M.P. Treatment of varicose and telangiectatic leg veins: double-blind prospective comparative trial between aethoxyskerol and sotradecol. Dermatol Surg. 2002;28(1):52–55. https://doi.org/10.1046/j.1524-4725.2002.01190.x.

11. Leach B.C., Goldman M.P. Comparative trial between sodium tetradecyl sulfate and glycerin in the treatment of telangiectatic leg veins. Dermatol Surg. 2003;29(6):612–614. https://doi.org/10.1046/j.1524-4725.2003.29148.x.

12. Kern P., Ramelet A.A., Wutschert R., Bounameaux H., Hayoz D. Single-blind, randomized study comparing chromated glycerin, polidocanol solution, and polidocanol foam for treatment of telangiectatic leg veins. Dermatol Surg. 2004;30(3):367–372. https://doi.org/10.1111/j.1524-4725.2004.30102.x.

13. Santoro P., Blandamura M., Chiti D., Scaramuzzino L. Postsclerotherapy occurrance of hyperpigmentation and other local and systemical signs in the treatment of small vessels varices with different sclerotherapic agents. Preliminary report. Acta Phlebologica. 2001;2(1):43–49. Available at: https://www.minervamedica.it/en/journals/acta-phlebologica/article.php?cod=R43Y2001N01A0043.

14. Chatard H., Dufour H. Note sur la nature mixte, hématique et mélanique, des pigmentations en phlébologie. Phlebologie. 1983;36(4):303–306. Available at: https://pubmed.ncbi.nlm.nih.gov/6657746/.

15. Goldman M.P., Kaplan R.P., Duffy D.M. Postsclerotherapy hyperpigmentation: a histologic evaluation. J Dermatol Surg Oncol. 1987;13(5):547–550. https://doi.org/10.1111/j.1524-4725.1987.tb00940.x.

16. Chatard H. Pigmentations post-sclérothérapiques. Phlebologie. 1976;29(3-4):211–216. Available at: https://pubmed.ncbi.nlm.nih. gov/1005503/.

17. Cuttell P.J., Fox J.A. The aetiology and treatment of varicose pigmentation. Phlebologie. 1982;35(1):381–389. Available at: https://pubmed.ncbi.nlm.nih.gov/7071186/.

18. Majno G., Palade G.E., Schoefl G.I. Studies on inflammation. II. The site of action of histamine and serotonin along the vascular tree: a topographic study. J Biophys Biochem Cytol. 1961;11(3):607–626. https://doi.org/10.1083/jcb.11.3.607.

19. Grega G.J., Svensjö E., Haddy F.J. Macromolecular permeability of the micro-vascular membrane-physiological and pharmacological regulation. Microcirculation. 1982;1(4):325–341.

20. Bessis M. Living blood cells and their ultrastructure. Berlin: Springer-Verlag; 1973. 767 p.

21. Leu H.J., Wenner A., Spycher M.A., Brunner U. Veränderungen der transendothelialen Permeabilität als Ursache des Odems bei der chronisch-venösen Insuffizienz. Med Welt. 1980;31(21):781–785. Available at: https://pubmed.ncbi.nlm.nih.gov/6993840/.

22. Bessis M., Lessin L.S., Beutler E. Morphology of the erythron. In: Williams W.J., Beutler E., Erslev A.J., Lichtman M.A. (eds.). Hematology. 3rd ed. New York, St. Louis, San Francisco: McGraw-Hill; 1983, pp. 257–279.

23. Goldman M.P., Bergan J.B., Guex J.J. Sclerotherapy. Treatment of varicose and telangiectatic leg veins: diagnosis and treatment. 4th ed. London: Mosby Elsevier; 2007.

24. Rabe E., Breu F.X., Flessenkämper I., Gerlach H., Guggenbichler S., Kahle B. et al. Leitlinie Sklerosierungsbehandlung der Varikose: S2k-Leitlinie der Deutschen Gesellschaft für Phlebologie (DGP) in Kooperation mit folgenden Fachgesellschaften: DDG, DGA, DGG, BVP. Hautarzt. 2021;72(1):50–64. https://doi.org/10.1007/s00105-020-04707-y.

25. Alòs J., Carreño P., López J.A., Estadella B., Serra-Prat M., Marinel-Lo J. Efficacy and safety of sclerotherapy using polidocanol foam: a controlled clinical trial. Eur J Vasc Endovasc Surg. 2006;31(1):101–107. https://doi.org/10.1016/j.ejvs.2005.08.018.

26. Jia X., Mowatt G., Burr J.M., Cassar K., Cook J., Fraser C. Systematic review of foam sclerotherapy for varicose veins. Br J Surg. 2007;94(8):925–936. https://doi.org/10.1002/bjs.5891.

27. Brunken A., Rabe E., Pannier F. Changes in venous function after foam sclerotherapy of varicose veins. Phlebology. 2009;24(4):145–150. https://doi.org/10.1258/phleb.2009.008068.

28. Goldman M.P., Guex J.J., Weiss R.A. Sclerotherapy. Treatment of varicose and telangiectatic leg veins. 5th ed. Philadelphia: Saunders Elsevier; 2011. 29. Yiannakopoulou E. Safety Concerns for Sclerotherapy of Telangiectases, Reticular and Varicose Veins. Pharmacology. 2016;98(1-2):62–69. https://doi.org/10.1159/000445436.

29. Ackerman Z., Seidenbaum M., Loewenthal E., Rubinow A. Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease. Arch Dermatol. 1988;124(9):1376–1378. https://doi.org/10.1001/archderm.1988.01670090032006.

30. Thibault P.K., Wlodarczyk J. Correlation of serum ferritin levels and postsclerotherapy pigmentation. A prospective study. J Dermatol Surg Oncol. 1994;20(10):684–686. https://doi.org/10.1111/j.1524-4725.1994.tb00453.x.

31. Scott C., Seiger E. Postsclerotherapy pigmentation. Is serum ferritin level an accurate indicator? Dermatol Surg. 1997;23(4):281–282. https://doi.org/10.1111/j.1524-4725.1997.tb00044.x.

32. Scultetus A.H., Villavicencio J.L., Kao T.C., Gillespie D.L., Ketron G.D., Iafrati M.D. et al. Microthrombectomy reduces postsclerotherapy pigmentation: multicenter randomized trial. J Vasc Surg. 2003;38(5):896–903. https://doi.org/10.1016/s0741-5214(03)00920-0.

33. Björk J., Goldschmidt T., Smedegård G., Arfors K.E. Methylprednisolone acts at the endothelial cell level reducing inflammatory responses. Acta Physiol Scand. 1985;123(2):221–224. https://doi.org/10.1111/j.1748-1716.1985.tb07581.x.

34. Clemetson C.A., Blair L., Brown A.B. Capillary strength and the menstrual cycle. Ann N Y Acad Sci. 1962;93:279–299. https://doi.org/ 10.1111/j.1749-6632.1962.tb30520.x.

35. Diaz A., Laufer M.R., Breech L.L. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006;118(5):2245–2250. https://doi.org/10.1542/peds.2006-2481.

36. Bowen A.R., McCalmont T.H. The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatol. 2007;57(5):836–839. https://doi.org/10.1016/j.jaad.2007.04.028.

37. White S.W., Besanceney C. Systemic pigmentation from tetracycline and minocycline therapy. Arch Dermatol. 1983;119(1):1–2. https://doi.org/10.1001/archderm.119.1.1.

38. Madan V., Lear J.T. Minocycline-induced pigmentation of pre-existing capillaritis. Br J Dermatol. 2007;156(3):590–591. https://doi.org/10.1111/j.1365-2133.2007.07680.x.

39. Goldman M.P. My sclerotherapy technique for telangiectasia and reticular veins. Dermatol Surg. 2010;36(Suppl. 2):1040–1045. https://doi.org/10.1111/j.1524-4725.2009.01408.x.

40. Weiss M.A., Hsu J.T., Neuhaus I., Sadick N.S., Duffy D.M. Consensus for sclerotherapy. Dermatol Surg. 2014;40(12):1309–1318. https://doi.org/10.1097/DSS.0000000000000225.

41. Wu A., Mansfield A.O. The morphological changes of the endothelium to venous stasis as observed under the scanning electron microscope. J Cardiovasc Surg (Torino). 1980;21(2):193–202. Available at: https://pubmed.ncbi.nlm.nih.gov/7364863/.

42. Leu H.J., Wenner A., Spycher M.A. Erythrocyte diapedesis in venous stasis syndrome. (Electron microscopic examinations). Vasa. 1981;10(1):17–23. Available at: https://pubmed.ncbi.nlm.nih.gov/7234118/.

43. Durán W., Pappas P.J., Schmid-Schönbein G.W. Microcirculatory inflammation in chronic venous insufficiency: current status and future directions. Microcirculation. 2000;7(6 Pt 2):S49–58. Available at: https://pubmed.ncbi.nlm.nih.gov/11151972/.

44. Goldman M.P., Sadick N.S., Weiss R.A. Cutaneous necrosis, telangiectatic matting, and hyperpigmentation following sclerotherapy. Etiology, prevention, and treatment. Dermatol Surg. 1995;21(1):19–29. https://doi.org/10.1111/j.1524-4725.1995.tb00107.x.

45. Mlosek R.K., Woźniak W., Malinowska S., Migda B., Serafin-Król M., Miłek T. The removal of post-sclerotherapy pigmentation following sclerotherapy alone or in combination with crossectomy. Eur J Vasc Endovasc Surg. 2012;43(1):100–105. https://doi.org/10.1016/j.ejvs.2011.10.005.

46. Bissett D.L., Oelrich D.M., Hannon D.P. Evaluation of a topical iron chelator in animals and in human beings: short-term photoprotection by 2-furildioxime. J Am Acad Dermatol. 1994;31(4):572–578. https://doi.org/10.1016/s0190-9622(94)70218-7.

47. Bissett D.L., McBride J.F. Synergistic topical photoprotection by a combination of the iron chelator 2-furildioxime and sunscreen. J Am Acad Dermatol. 1996;35(4):546–549. https://doi.org/10.1016/s0190-9622(96)90677-5.

48. Bogachev V.Yu., Kuznetsov M.R., Lobanov V.N., Turkin P.Yu. Cryocompression sclerotherapy of reticular veins and telangiectasias. Angiology and Vascular Surgery. 2018;24(3):92–98. (In Russ.) Available at: https://www.angiol.ru/patrns/pdf/2018/angiol-2018-3.pdf.

49. De Souza M. das G.C., Cyrino F.Z., Mayall M.R., Virgini-Magalhães C.E., Sicuro F.L., de Carvalho J.J. et al. Beneficial effects of the micronized purified flavonoid fraction (MPFF, Daflon® 500mg) on microvascular damage elicited by sclerotherapy. Phlebology. 2016;31(1):50–56. https://doi.org/10.1177/0268355514564414.

50. Bogachev V.Yu., Boldin B.V., Lobanov V.N. Benefits of micronized purified flavonoid fraction as adjuvant therapy on inflammatory response after sclerotherapy. Int Angiol. 2018;37(1):71–78. https://doi.org/10.23736/S0392-9590.17.03868-8.

51. Bogachev V.Yu., Boldin B.V., Turkin P.Yu. Administration of Micronized Purified Flavonoid Fraction During Sclerotherapy of Reticular Veins and Telangiectasias: Results of the National, Multicenter, Observational Program VEIN ACT PROLONGED-C1. Adv Ther. 2018;35(7):1001–1008. https://doi.org/10.1007/s12325-018-0731-z.

52. Seeley B.M., Denton A.B., Ahn M.S., Maas C.S. Effect of homeopathic Arnica montana on bruising in face-lifts: results of a randomized, double-blind, placebo-controlled clinical trial. Arch Facial Plast Surg. 2006;8(1):54–59. https://doi.org/10.1001/archfaci.8.1.54.

53. Iannitti T., Morales-Medina J.C., Bellavite P., Rottigni V., Palmieri B. Effectiveness and Safety of Arnica montana in Post-Surgical Setting, Pain and Inflammation. Am J Ther. 2016;23(1):e184–197. https://doi.org/10.1097/MJT.0000000000000036.

54. Bogachev V.Yu., Boldin B.V., Turkin P.Yu., Lobanov V.N. Local drugs in treating and decreasing the incidence of adverse reactions after sclerotherapy of telangiectasia. Angiology and Vascular Surgery. 2019;25(4):102–107. (In Russ.) https://doi.org/10.33529/ANGIO2019405.

55. Bogachev V.Yu., Rosukhovskiy D.A., Borsuk D.A., Shonov O.A., Mandzhikyan O.P., Lobastov K.V. et al. Russian clinical practice guidelines for the management of C1 clinical class of chronic venous disorders (reticular veins and telangiectasias). Ambulatornaya Khirurgiya. 2020;(3-4):140–206. (In Russ.) https://doi.org/10.21518/18/1995-1477-2020-3-4-140-206.

56. Goldman M.P., Beaudoing D., Marley W., Lopez L., Butie A. Compression in the treatment ofleg telangiectasia: a preliminary report. J Dermatol Surg Oncol. 1990;16(4):322–325. https://doi.org/10.1111/j.1524-4725.1990.tb00042.x.

57. Weiss R.A., Sadick N.S., Goldman M.P., Weiss M.A. Post-sclerotherapy compression: controlled comparative study of duration of compression and its effects on clinical outcome. Dermatol Surg. 1999;25(2):105–108. https://doi.org/10.1046/j.1524-4725.1999.08180.x.

58. Mosti G. Post-treatment compression: duration and techniques. Phlebology. 2013;28(Suppl. 1):21–24. https://doi.org/10.1177/0268355513475955.

59. Cuttell P.J., Fox J.A. The aetiology and treatment of varicose pigmentation. Phlebologie. 1982;35(1):381–389. Available at: https://pubmed.ncbi.nlm.nih.gov/7071186/.

60. Palm M.D., Guiha I.C., Goldman M.P. Foam sclerotherapy for reticular veins and nontruncal varicose veins of the legs: a retrospective review of outcomes and adverse effects. Dermatol Surg. 2010;36(Suppl. 2):1026–1033. https://doi.org/10.1111/j.1524-4725.2010.01496.x.

61. Gonzalez Ochoa A.J., Carrillo J., Manríquez D., Manrique F., Vazquez A.N. Reducing hyperpigmentation after sclerotherapy: A randomized clinical trial. J Vasc Surg Venous Lymphat Disord. 2021;9(1):154–162. https://doi.org/10.1016/j.jvsv.2020.06.019.

62. Goldman M.P., Weiss R.A. Sclerotherapy. Treatment of Varicose and Telangiectatic Leg Veins. 6th ed. Elsevier; 2017. 464 p.

63. Tafazzoli A., Rostan E.F., Goldman M.P. Q-switched ruby laser treatment for postsclerotherapy hyperpigmentation. Dermatol Surg. 2000;26(7):653–656. https://doi.org/10.1046/j.1524-4725.2000.99268.x.

64. Hamilton H.K., Dover J.S., Arndt K.A. Successful treatment of disfiguring hemosiderin-containing hyperpigmentation with the Q-switched 650-nm wavelength laser. JAMA Dermatol. 2014;150(11):1221–1222. https://doi.org/10.1001/jamadermatol.2014.1838.

65. Lloyd A.A., Graves M.S., Ross E.V. Cutaneous siderosis secondary to intramuscular iron dextran treated with 755nm Q-switched alexandrite laser: A case report. Lasers Surg Med. 2015;47(5):386–387. https://doi.org/10.1002/lsm.22353.

66. Wong M., Parsi K., Myers K., De Maeseneer M., Caprini J., Cavezzi A. et al. Sclerotherapy oflower limb veins: Indications, contraindications and treatment strategies to prevent complications – A consensus document of the International Union of Phlebology-2023. Phlebology. 2023:2683555231151350. https://doi.org/10.1177/02683555231151350.

67. Burnand K., Clemenson G., Morland M., Jarrett P.E., Browse N.L. Venous lipodermatosclerosis: treatment by fibrinolytic enhancement and elastic compression. Br Med J. 1980;280(6206):7–11. https://doi.org/10.1136/bmj.280.6206.7.

68. Helfman T., Falanga V. Stanozolol as a novel therapeutic agent in dermatology. J Am Acad Dermatol. 1995;33(2 Pt 1):254–258. https://doi.org/10.1016/0190-9622(95)90244-9.

69. Rabe E., Partsch H., Hafner J., Lattimer C., Mosti G., Neumann M. et al. Indications for medical compression stockings in venous and lymphatic disorders: An evidence-based consensus statement. Phlebology. 2018;33(3):163–184. https://doi.org/10.1177/0268355516689631.

70. Aydın U., Engin M., Türk T., Ata Y. The effectiveness of different treatment methods in isolated telangiectasia and reticular vein treatment: A single-center prospective randomized study. Phlebology. 2022;37(1):26–32. https://doi.org/10.1177/02683555211030739.

71. Finlayson K.J., Parker C.N., Miller C., Edwards H.E., Campbell J. Decreased mobility, lack of social support, haemosiderosis and use of antidepressant medications may predict recurrent venous leg ulcers within 12 months of healing: A prospective longitudinal study. Phlebology. 2022;37(3):206–215. https://doi.org/10.1177/02683555211063986.

72. Suehiro K., Morikage N., Harada T., Takeuchi Y., Mizoguchi T., Ike S. et al. Post-treatment course of acute lipodermatosclerosis. Phlebology. 2023;38(2):73–79. https://doi.org/10.1177/02683555221147473.

73. Willital G.H., Heine H. Efficacy of Contractubex gel in the treatment of fresh scars after thoracic surgery in children and adolescents. Int J Clin Pharmacol Res. 1994;14(5-6):193–202. Available at: https://pubmed.ncbi.nlm.nih.gov/7672876/.

74. Sidgwick G.P., McGeorge D., Bayat A. A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring. Arch Dermatol Res. 2015;307(6):461–477. https://doi.org/10.1007/s00403-015-1572-0.

75. Phan T.T., Lim I.J., Sun L., Chan S.Y., Bay B.H., Tan E.K., Lee S.T. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci. 2003;33(3):192–194. https://doi.org/10.1016/j.jdermsci.2003.08.008.

76. Phan T.T., Lim I.J., Chan S.Y., Tan E.K., Lee S.T., Longaker M.T. Suppression of transforming growth factor beta/smad signaling in keloidderived fibroblasts by quercetin: implications for the treatment of excessive scars. J Trauma. 2004;57(5):1032–1037. https://doi.org/10.1097/01.ta.0000114087.46566.eb.

77. Willital G.H., Simon J. Efficacy of early initiation of a gel containing extractum cepae, heparin, and allantoin for scar treatment: an observational, noninterventional study of daily practice. J Drugs Dermatol. 2013;12(1):38–42. Available at: https://pubmed.ncbi.nlm.nih.gov/23377326/.

78. Ho W.S., Ying S.Y., Chan P.C., Chan H.H. Use of onion extract, heparin, allantoin gel in prevention of scarring in Chinese patients having laser removal of tattoos: a prospective randomized controlled trial. Dermatol Surg. 2006;32(7):891–896. https://doi.org/10.1111/j.1524-4725.2006.32192.x.

79. Minaev S.V., Vladimirova O.V., Kirgizov I.V., Akselrov M.A., Razin M.P., Ivchenko A.A. et al. Multicenter study of the effectiveness of antiscar therapy in patients at different age periods. Pirogov Russian Journal of Surgery. 2020;(9):51–59. (In Russ.) Available at: https://www.mediasphera.ru/issues/khirurgiya-zhurnal-im-n-i-pirogova/2020/9/1002312072020091051?ysclid=lgw4g6xwul178979019.