Differentiating Arteriolosclerotic Ulcers of Martorell from Other Types of Leg Ulcers Based on Vascular Histomorphology

Authors

  • Julia Deinsberger
  • Jonas Brugger
  • Philipp Tschandl
  • Barbara Meier-Schiesser
  • Florian Anzengruber
  • Simon Bossart
  • Stanislava Tzaneva
  • Peter Petzelbauer
  • Kornelia Böhler
  • Helmut Beltraminelli
  • Jürg Hafner
  • Benedikt Weber Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria

DOI:

https://doi.org/10.2340/00015555-3804

Keywords:

arteriolosclerosis, Martorell, leg ulcer, histomorphology, hyalinosis

Abstract

Clinical differential diagnosis of arteriolosclerotic ulcers of Martorell is challenging due to the lack of clearly affirmative instrument-based diagnostic criteria. The aim of this study was to develop vascular histomorphological diagnostic criteria differentiating Martorell ulcers from other types of leg ulcers. The histomorphology of patients diagnosed with arteriolosclerotic ulcers of Martorell (n = 67) was compared with that of patients with venous leg ulcers, necrotizing leukocytoclastic vasculitis, pyoderma gangrenosum, and non-ulcerative controls (n = 15 each). In a multivariable logistic regression model, the rates of arteriolar calcification (odds ratio (OR) 42.71, 95% confidence interval (CI) 7.43–443.96, p < 0.001) and subendothelial hyalinosis (OR 29.28, 95% CI 4.88–278.21, p <0.001) were significantly higher in arteriolosclerotic ulcers of Martorell. Arteriolar cellularity was significantly lower in Martorell ulcers than in controls (OR 0.003, 95 CI < 0.001–0.97, p = 0.05). However, the wall-to-lumen ratio was similar in all ulcers (OR 0.975, 95% CI 0.598–2.04, p =0.929). Based on the Youden index, a wall cellularity of < 0.24 cells/100 μm2 was determined as the optimum cut-off point (sensitivity 0.955, specificity 0.944). Thus, arteriolar calcification, subendothelial hyalinosis, and arteriolar cellularity revealed high discriminatory power for arteriolosclerotic ulcers of Martorell.

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References

Alavi A, Mayer D, Hafner J, Sibbald RG. Martorell hypertensive ischemic leg ulcer: an underdiagnosed Entity(c). Adv Skin Wound Care 2012; 25: 563-572; quiz 573-564.

DOI: https://doi.org/10.1097/01.ASW.0000423442.08531.fb

Mekkes JR, Loots MA, Van Der Wal AC, Bos JD. Causes, investigation and treatment of leg ulceration. Br J Dermatol 2003; 148: 388-401.

DOI: https://doi.org/10.1046/j.1365-2133.2003.05222.x

Martinengo L, Olsson M, Bajpai R, Soljak M, Upton Z, Schmidtchen A, et al. Prevalence of chronic wounds in the general population: systematic review and meta-analysis of observational studies. Ann Epidemiol 2019; 29: 8-15.

DOI: https://doi.org/10.1016/j.annepidem.2018.10.005

Martorell F. Ulcus cruris hypertonicum. Med Klin 1957; 52: 1945-1946.

Martorell F. Hypertensive ulcer of the leg. J Cardiovasc Surg (Torino) 1978; 19: 599-600.

Vuerstaek JD, Reeder SW, Henquet CJ, Neumann HA. Arteriolosclerotic ulcer of Martorell. J Eur Acad Dermatol Venereol 2010; 24: 867-874.

DOI: https://doi.org/10.1111/j.1468-3083.2009.03553.x

Hafner J, Nobbe S, Partsch H, Lauchli S, Mayer D, Amann-Vesti B, et al. Martorell hypertensive ischemic leg ulcer: a model of ischemic subcutaneous arteriolosclerosis. Arch Dermatol 2010; 146: 961-968.

DOI: https://doi.org/10.1001/archdermatol.2010.224

Salcido RS. Enduring eponyms: the mystery of the Martorell ulcer. Adv Skin Wound Care 2012; 25: 535.

DOI: https://doi.org/10.1097/01.ASW.0000423433.03586.a6

Rouphael NG, Ayoub NM, Tomb RR. Skin ulcers misdiagnosed as pyoderma gangrenosum. N Engl J Med 2003; 348: 1064-1066; author reply 1064-1066.

DOI: https://doi.org/10.1056/NEJM200303133481118

Malhi HK, Didan A, Ponosh S, Kumarasinghe SP. Painful leg ulceration in a poorly controlled hypertensive patient: a case report of martorell ulcer. Case Rep Dermatol 2017; 9: 95-102.

DOI: https://doi.org/10.1159/000468977

Graves JW, Morris JC, Sheps SG. Martorell's hypertensive leg ulcer: case report and concise review of the literature. J Hum Hypertens 2001; 15: 279-283.

DOI: https://doi.org/10.1038/sj.jhh.1001154

Kolios AGA, Hafner J, Luder C, Guenova E, Kerl K, Kempf W, et al. Comparison of pyoderma gangrenosum and Martorell hypertensive ischaemic leg ulcer in a Swiss cohort. Br J Dermatol 2018; 178: e125-e126.

DOI: https://doi.org/10.1111/bjd.15901

Hafner J. Calciphylaxis and Martorell hypertensive ischemic leg ulcer: same pattern - one pathophysiology. Dermatology 2016; 232: 523-533.

DOI: https://doi.org/10.1159/000448245

Henderson CA, Highet AS, Lane SA, Hall R. Arterial hypertension causing leg ulcers. Clin Exp Dermatol 1995; 20: 107-114.

DOI: https://doi.org/10.1111/j.1365-2230.1995.tb02666.x

Serpa MJ, Franco S, Repolho D, Araujo I, Mateus S, Baptista AM, et al. A challenging diagnosis of leg ulcer. Eur J Case Rep Intern Med 2018; 5: 000952.

DOI: https://doi.org/10.12890/2018_000952

Leu HJ. Hypertensive ischemic leg ulcer (Martorell's ulcer): a specific disease entity? Int Angiol 1992; 11: 132-136.

Lima Pinto AP, Silva NA, Jr, Osorio CT, Rivera LM, Carneiro S, Ramos ESM, et al. Martorell's ulcer: diagnostic and therapeutic challenge. Case Rep Dermatol 2015; 7: 199-206.

DOI: https://doi.org/10.1159/000430884

Hines EA, Jr., Farber EM. Ulcer of the leg due to arteriolosclerosis and ischemia, occurring in the presence of hypertensive disease (hypertensive-ischemic ulcers). Proc Staff Meet Mayo Clin 1946; 21: 337-346.

Schnier BR, Sheps SG, Juergens JL. Hypertensive ischemic ulcer. A review of 40 cases. Am J Cardiol 1966; 17: 560-565.

DOI: https://doi.org/10.1016/0002-9149(66)90247-5

Shutler SD, Baragwanath P, Harding KG. Martorell's ulcer. Postgrad Med J 1995; 71: 717-719.

DOI: https://doi.org/10.1136/pgmj.71.842.717

Monfort JB, Cury K, Moguelet P, Chasset F, Bachmeyer C, Frances C, et al. Cutaneous arteriolosclerosis is not specific to ischemic hypertensive leg ulcers. Dermatology 2018; 234: 194-197.

DOI: https://doi.org/10.1159/000492669

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310: 2191-2194.

DOI: https://doi.org/10.1001/jama.2013.281053

Farber EM, Hines EA. The arterioles of the skin in essential hypertension. J Invest Dermatol 1947; 9: 285-298.

DOI: https://doi.org/10.1038/jid.1947.101

Armstrong RA. When to use the Bonferroni correction. Ophthalmic Physiol Opt 2014; 34: 502-508.

DOI: https://doi.org/10.1111/opo.12131

Team RC. A Language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2019. [Accessed December 18, 2019] Available from: https://www.R-project.org/.

Selvaraju RR, Cogswell M, Das A, Vedantam R, Parikh D, Batra D. Grad-CAM: Visual Explanations from Deep Networks via Gradient-Based Localization. Avaliable from: https://ieeexplore.ieee.org/document/8237336. 2017 IEEE International Conference on Computer Vision (ICCV). Venice, 2017: p. 618-626.

DOI: https://doi.org/10.1109/ICCV.2017.74

Gamble CN. The pathogenesis of hyaline arteriolosclerosis. Am J Pathol 1986; 122: 410-420.

Mencke R, Umbach AT, Wiggenhauser LM, Voelkl J, Olauson H, Harms G, et al. Klotho deficiency induces arteriolar hyalinosis in a trade-off with vascular calcification. Am J Pathol 2019; 189: 2503-2515.

DOI: https://doi.org/10.1016/j.ajpath.2019.08.006

Dagregorio G, Guillet G. A retrospective review of 20 hypertensive leg ulcers treated with mesh skin grafts. J Eur Acad Dermatol Venereol 2006; 20: 166-169.

DOI: https://doi.org/10.1111/j.1468-3083.2006.01399.x

De Andres J, Villanueva VL, Mazzinari G, Fabregat G, Asensio JM, Monsalve V. Use of a spinal cord stimulator for treatment of Martorell hypertensive ulcer. Reg Anesth Pain Med 2011; 36: 83-86.

DOI: https://doi.org/10.1097/AAP.0b013e31820308b2

Conde Montero E, Guisado Munoz S, Perez Jeronimo L, Peral Vazquez A, Montoro Lopez JJ, Hocajada Reales C, et al. Martorell hypertensive ischemic ulcer successfully treated with punch skin grafting. Wounds 2018; 30: E9-E12.

Nigwekar SU, Bloch DB, Nazarian RM, Vermeer C, Booth SL, Xu D, et al. Vitamin K-dependent carboxylation of matrix gla protein influences the risk of calciphylaxis. J Am Soc Nephrol 2017; 28: 1717-1722.

DOI: https://doi.org/10.1681/ASN.2016060651

Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997; 386: 78-81.

DOI: https://doi.org/10.1038/386078a0

Schurgers LJ, Uitto J, Reutelingsperger CP. Vitamin K-dependent carboxylation of matrix Gla-protein: a crucial switch to control ectopic mineralization. Trends Mol Med 2013; 19: 217-226.

DOI: https://doi.org/10.1016/j.molmed.2012.12.008

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Published

2021-05-04

How to Cite

Deinsberger, J., Brugger, J., Tschandl, P., Meier-Schiesser, B., Anzengruber, F., Bossart, S., Tzaneva, S., Petzelbauer, P., Böhler, K., Beltraminelli, H., Hafner, J., & Weber, B. (2021). Differentiating Arteriolosclerotic Ulcers of Martorell from Other Types of Leg Ulcers Based on Vascular Histomorphology. Acta Dermato-Venereologica, 101(5), adv00449. https://doi.org/10.2340/00015555-3804