2004, Number 3
Histopathological Studies in Lipodermatosclerosis Associated with Venous Hypertension. Pathophysiological Considerations
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ABSTRACTLipodermatosclerosis (LDS) or sclerosing panniculitis is an induration of the dermis, hypodermis and sometimes the superficial fascia. It is a chronic inflammatory process usually related to venous pathology, with neo-vascularization, adipose tissue necrosis and fibrosis. Several hypotheses have been proposed, but the exact mechanism is still unknown. In this paper we studied the skin biopsies of 6 patients with chronic LDS. We performed histochemical techniques, immunolabelling of methalloproteinases 1, 2 and 3; CD68, alpha smooth muscle actin and plastic semithin sections. Our main findings were: venous vessels were altered, with narrow lumens intimal fibrosis and hyperplasia, some arterial vessels also showed fragmentation and reduplication of internal elastic layer with subintimal fibrosis. There was a remarkable disorganization of reticular and hypodermal layer due to a intense fibrosis. Typical area of pseudomembranous fatty necrosis and pseudocyst were observed. There were patchy mixed inflammatory infiltrates in all skin layers involved. Methalloproteinases 1, 2 and 3 were positive in epidermis, endothelial cells, in some dermal and hypodermal cells, outlining pseudocysts and in pseudomembranous fat necrosis. In plastic semithin sections the presence of lipids droplets permeating between collagen fibers even in superficial dermis were evident.
Jorizzo JL, White WL, Zanolli MD, Greer KE, et al. Sclerosing panniculitis. A clinicopathologic assesment. Arch Dermatol 1991; 127: 554-8.
Kirsner RS, Pardes JB, Eagelstein WH, Falange V. The clinical spectrum of lipodermatosclerosis. J Am Acad Dermatol 1993; 28: 623-7.
Nazchitz JE, Yeshurun D, Misselevich I, Boss JH. The pathogenesis of lipodermatosclerosis: facts, uncertainties amd theories. J Eur Acad Dermatol Venereol 1997; 9: 209-14.
Greemberg AS, Hasan A, Montalvo BM, Falabella A, et al.Acute lipodermatosclerosisis associated with venous insufficiency. J Am Acad Dermatol 1996; 35: 566-8.
Bruce AJ, Bennett DD, Lohse ChM, Rooke TW, et al. Lipodermatosclerosis: Review of cases evaluated at Mayo Clinic. J Am Acad Dermatol 2002; 46: 187-92.
Herouy Y, May AE, Pornschlegel G, Stetter Ch, et al. Lipodermatosclerosis is characterized by elevated expression and activation of matrix metalloproteinases: implications for venous ulcer formation. J Invest Dermatol 1998; 111: 822-7.
Diaz Cascajo C, Borghi S. Subcutaneous pseudomembranous fat necrosis: new observations J Cutan Pathol 2002; 29: 5-10.
Valencia IC, Falabella A, Kirsner RS, Eagelstein WH. Chronic venous insufficiencyand venous ulceration. J Am Acad Dermatol 2001; 44: 401 -21.
Shi SR, Key ME, Kalkra KL. Antigen retrieval in formalin fixed and paraffin embedded tissues. An enhancement method for immunohistochemical staining on microwave oven heating of tissue section. J Histochem Cytochem 1991; 39: 741-8.
Coleridge Smith PD. Deleterious effects of white cells in the course of skin damage in CVI. Int Angiol 2002; 21: 26-32.
Oda M, han JY, Nakamura M. Endothelial cell dysfunction in microvasculature: relevance to disease processes. Clin Hemorheol Microcirc 2000; 23: 199-211.
Leu HJ. Morphology of chronic venous insufficiency- Light and electron microscopic examination. Vasa 1991; 20: 330-42.
Sahary M, Shields DA, Porter JB, Scurr JM, et al. Leucocyte activity in the microcirculation of the legs in patients with chronic venous disease. J Vasc Surg 1997; 26: 265-73.
Carpentier PH. Role of leukocytes in the pathogenesis of trophic venous disorders. J Mal Vasc 1998; 23: 274-6.
Bergan JJ, Schmif-Schonbein GW, Takase S. Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500 mg. Angiology 2001; 52: 43-7.
Herouy Y, Aizpurua J, Stetter C, Dichmann S, et al. The role of the urokinase-type plasminogen activator (uPA) and its receptor (CD87) in lipodermatosclerosis. J Cutan Pathol 2001; 28: 291-7.
Chabrier PE. Growth factors and vascular wall. Int Angiol 1996; 15: 100-3.
Peschen M, Grenz H, Grothe C, Schöpf E, et al. Patterns of epidermal growth factor receptor, basic fibroblast growth factor and transforming growth factor-Beta 3 expression in skin with chronic venous insufficiency. Eur J Dermatol 1998; 8: 334-8.
Naschitz JE, Sabo E, Yeshurun D, Gilhar A, et al. An experimental model of fascitis-panniculitis. Induction of chronic fibrosis panniculitis in the rat by subcutaneous injections of lipase. Isr J Med Sci 1996; 32: 1078-85.
Naschitz JE, Bejar J, Mogilner J, Misselevich I, et al. Acute lipase-induced panniculitis in rats with ligated veins of the hindlimb: a contribution of the role of acute panniculitis as a precursor of lipodermatosclerosis of venous disease. J Dermatol Sci 1999; 19: 9-16.
Cornelius LA, Nehring LC, Roby JD, Parlos WC, et al. Human dermal microvascular endothelial cells produce matrix metalloproteinases in response to angiogenic factors and migration. J Invest Dermatol 1995; 105: 170-6.
Tamai K, Ishikawa H, Mauviel A, Uitto J. Interferon-Gama coordinately upregulates matrix metalloproteinases (MMP) -1 and MMP-3, but not tissue inhibitor of metalloproteinases (TIMP), expression in cultured keratinocytes. J Invest Dermatol 1995; 104: 384-90.
Vaalamo M, Weckroth M, Poulakkainen P, Kere J, et al. Patterm of matrix metalloproteinases and TIMP-1 expression in chronic and normally healing human cutaneous wounds. Br J Dermatol 1996; 135: 52-9.
Kähäri VM, Saarialho-Kere U. Matrix metalloproteinases in skin. Exp Dermatol 1997; 6: 199-213.
Herouy Y, Trefzer D, Zimpfer U, Schöpf E, et al. Matrix metalloproteinases and venous leg ulceration. Eur J Dermatol 2000; 9: 173-80.
Herrick SE, Sloan P, McGurk M, Freak L, et al.Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers. Am J Pathol 1992; 141: 1085-95.
Knauper V, Murphy G, Tschesche H. Activation of human neutrophil procollagenase by stromelysin 2. Eur J Biochem 1996; 15: 187-91.
Wysocki AB, Staiano-Coico L, Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 1993; 101: 64-8.
Konttinen YT. Matrix metalloproteinases, gelatinases and collagenases in chronic leg ulcers. J Invest dermatol 1996; 106: 1119-24.
Herouy Y, Nochowschi P, Schöpf E, Norgauer J. Lipodermatosclerosis and the significance of proteolytic remodeling in the pathogenesis of venous ulceration. Int Mol Med 1999; 3: 511-5.
Norgauer J, Hildenbrand T, Idzko M, Panther E, et al. Elevated expression of extracellular matrix metalloproteinases inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers. Br J Dermatol 2002; 147: 1180-6.
Brinckmann J, Notbohm H, Tronnier M, Acil Y, et al. Overhydroxylation of lysil residues in the initial step for altered collagen cross-links and fibril architectures in fibrotic skin. J Invest Dermatol 1999; 113: 617-21.
Brinckmann J, Neess CM, Gaber Y, Sobhi H, et al. Diferent pattern of collagen cross-links in two sclerotic diseases: lipodermatosclerosis and circumscribed scleroderma. J Invest Dermatol 2001; 117:269-73.
Kim CS, Kawada T, Yoo H, Kwon BS, et al. Macrophage inflammatory protein-related-2, a novel CC chemolineca regulate preadipocyte migration and adipocyte differentiation. FEBS Lett 2003; 549: 125-30.
Chaldakov GN, Stankulov IS, Hristova M, Ghenev PI. Adipobiology of disease: adipokines and adipokine-targeted pharmacology. Curr Phar Des 2003; 9:1023-31.
Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, et al. The Biology of White Adipocyte Proliferation. Obesity Rev 2001; 2: 239-54.
Lilla J, Stickens D, Werb Z. Metalloproteases and adipogenesis: a weighty subject. Am J Pathol 2002; 160: 1551-4.
Sanchez Yus E, Huarte S, Sanz Vico MD. ¿Vena o Arteria? Una cuestión decisiva en la patología hipodérmica. Piel 1987; 2: 213-7.