Hypotheses and Comments © 1990 Kargcr AG. Basel 0011-9075/90/1814-0264 $2.75/0
Dermatológica 1990;181:264-265
Is There a Link between Dendrocytes, Fibrosis and Sclerosis? G.E. Piérard, ./. Arrese-Estrada, C. Piérard-Franchimont, F. Deleixhe-Mauhin Department of Dermatopathology. CHU du San Tilman. Liège, Belgium
Key Words. Fibrosis • Sclerosis ■Dendrocyte • Factor XII la • Scleroderma • Dermatofibroma • Scar • Keloid Abstract. In a series of fibrotie and sclerotic diseases including scars, keloids, fibromas, scleroderma and lichen sclerosuset atrophicus. we found modifications in the dendrocyte population. Dendrocytes were numerous in fibrotie dis eases associated with little deposits of collagen. Conversely, they were almost absent in sclerotic diseases when the laydown of collagen was prominent. We hypothesize that dendrocytes, by their content in factor XII la, may limit the accu mulation of collagen in the skin.
Scleroderma and Lichen sclerosus et atrophicus Scleroderma and lichen sclerosus et atrophicus are two sclerotic diseases, because the dermal cell density is decreased compared to normal skin [9]. Acrosclerodcrma is a diffuse process while lichen sclerosus et atrophicus and morphea are two disorders, respectively, limited to the superficial dermis and to circumscribed parts of the integument. In early acroscleroderma, and at the periphery of mor phea and lichen sclerosus et atrophicus, we found numer ous large dendrocytes [3, 6]. When deposits of collagen were evidenced in these diseases, dendrocytes were almost totally absent. Scleroderma is currently considered as a disease of the microvasculature [10]. If dendrocytes may be considered as cells of the microvasculature [6], their disappearance in scleroderma could reflect the primary vascular alterations. It has been reported that factor XIII may be an effec tive treatment for scleroderma [11, 12]. Recent reports have also shown that factor XII la inhibits the in vitro syn thesis of collagen by fibroblasts of normal skin and scler oderma [ 13, 14]. It is therefore possible that the cause of cutaneous sclerosis in scleroderma is linked to the defi ciency in factor-XIIIa-positivc dendrocytes.
Downloaded by: MacQuarie University 137.111.162.20 - 1/20/2020 12:15:35 AM
Accurate morphologic observations usually precede and lay the foundation for studies aimed at determining pathogenesis. It is now possible to revisit the concept of fibrosis and sclerosis and to throw light on the influence of dendrocytes in these diseases. Fibrosis in reparative lesions is defined by the accumu lation of resident connective tissue cells, often associated with newly formed vessels. Normal collagen bundles are replaced by fibrillary collagen. Conversely, sclerosis is defined by the presence of thickened, homogeneous collagen bundles with little cells and vessels interspersed between them. In the past, all spindle-shaped cells of the dermis were called fibroblasts or fibrocytes. Recently dendrocytes have been identified among them. They contain factor XHIa [1-7], and many of them are associated with the dermal microvasculature [6, 7J. These cells have phago cytic properties and could be involved in immunological functions [5,8]. Could they also be involved in the regula tion of collagen synthesis and degradation? We raise the hypothesis that there is an inverse rela tionship between the density of dendrocytes and the amount of collagen deposits. Examples of such a relation ship primarily concern scleroderma, lichen sclcrosus et atrophicus, scars, keloids and dermatofibromas.
Is There a Link between Dendrocytes, Fibrosis and Sclerosis?
Dendrocytes arc numerous in early scarring [3, 7] and in scars of longer duration when deposits of collagen arc poor [3]. Conversely, scars with a well-developed extracellular matrix and keloids are devoid of dendro cytes. It is known that Black people have a tendency to form keloids very easily. We have observed that the normal skin of Black people contains a lower number of dendro cytes than that of Caucasians. We have also observed that in White people dendrocytes arc more numer ous in the superficial dermis than in the deep dermis and arc also more numerous in sun-exposed areas than in sun-protected areas [8]. Photochemotherapy also in duces an accumulation of dendrocytes when photosclero sis is absent [15]. If these observations may be linked, we could consider that the amount of light reaching the dermis could modulate the number of dendrocytes. Furthermore, the natural tendency of Black people to develop keloids could be related to their relative dendrocyte deficiency related to the photoprotection by melanin.
Dermatofibromas Dermatofibromas basically represent fibrotic lesions. In rare instances, however, sclerosis may be found at the center of the lesions. Dendrocytes and endothelial cells represent the two main cell populations of ‘fibrotic dermatofibromas' [3, 4, 16]. Protein synthesis, in particular of collagen, is then poor in the dendrocytes [16]. In ‘sclerotic dermatofibro mas’, we have not identified dendrocytes in the sclerotic foci, and they were only confined to the periphery of the lesions.
Hypothesis It is striking that our observations of fibrotic and scle rotic diseases lead to the same findings without any excep tion. Fibrosis is a dendrocyte-rich condition, while sclero sis is a dendrocyte-poor condition. As several cell func tions are modulated by factor XIII, we frame as an hypothesis that dendrocytes, by their content in factor XHIa, may contribute to a limitation in the laydown of collagen in the dermis.
References 1 Ccrio R. Spaull JR. Wilson Jones E: Identification of factor XII la in cutaneous tissue. Histopathology 1988;13:362-363. 2 Nemeth AJ. Pcnneys JR. Bernstein I IB : Fibrous papule: A tumor of the fibrohistiocytic cells that contain factor XHIa. J Am Acad Dermatol 1988;19:1102-1106. 3 Arrese Estrada J. Laso Dosai F. Piérard-Franchimont C. Piérard GE: Heterogeneity in the cell population of the dermis; in Piérard GE. Piérard-Franchimont C (eds): The Dermis - Front Biology to Diseases. Liege. Publ Monographies Dermatopathologiques Lié geoises, 1989. pp 1-12. 4 Cerio R. Spaull JR. Wilson Jones E: Histiocytoma cutis: A tumour of dermal dendrocytes (dermal dendrocytoma). Br J Dermatol 1989:120:197-206. 5 Cerio R. Griffiths CEM. Cooper KD. Nickoloff BJ. Hcadington JT: Characterization of factor XII la positive dermal dendritic cells in normal and inflamed skin. Br J Dermatol 1989:121:421^131. 6 Arrese Estrada J. Piérard GE: Factor-XIIIa-positive dendrocytes and the dermal microvascular unit. Dermatológica 1990:180: 51-53. 7 PenneysNS: Factor XIII expression in the skin: Observationsand a hypothesis. J Am Acad Dermatol 1990:22:484-488. 8 Piérard-Franchimont C, Arrese Estrada J. Piérard GE: Dendro cytes. cellules de Langerhans et photovieillissement. Ann Dermatol Vénéréol. in press. 9 Piérard GE: I listo logical and rheological grading of cutaneous scle rosis in scleroderma. Dermatológica 1989; 179:18—20. 10 Leroy EC: The vascular defect in scleroderma (systemic sclerosis). Acta Med Scand 1987;S715:165-168. 11 Thivolct J. Perot H. McunicrF. Bouchet B: Action thérapeutique du facteur FXIII de la coagulation dans la sclérodermie. Nouv Presse Méd 1975:4:2779-2781. 12 Guillevin L. Euler-Ziegler L.Chouvet B. et al: Treatment with fac tor XI 11and long-term follow-upof 86 patients with progressive sys temic sclerosis. Presse Méd 1985:14:2327-2330. 13 Paye M, Nusgens BV, Lapièrc ChM: Factor XIII of blood coagula tion modulates collagen biosynthesis by fibroblasts in vitro. Hae mostasis 1989:19:274-283. 14 Paye M. Read D. Nusgens B. Lapièrc ChM: Factor XIII in scler oderma: In vitro studies. Br J Dermatol 1990:122:371-382. 15 Piérard-Franchimont C, Nickcls-Read D. Ben Mosbah T. Arrese Estrada J. Piérard GE: Early dermatopathological signs related to bath PUVA therapy. J Pathol, in press. 16 Piérard GE. Piérard-Franchimont C. Van Cauwenberge D. Mélotte P. Christophe J. Lapièrc ChM: Histiocytofibromc et fibromatose palmaire de Dupuytren. Etude autohistoradiographique comparative de leurs activités prolifératives et biosynthétiques. Ann Dermatol Vénéréol 1985;112:877-881.
Received: April 23. 1990 Accepted: April 28. 1990 Dr. G.E. Piérard D epartm ent of D erm atopathology
CHU du Sart Tilman B-4000 Liège (Belgium)
Downloaded by: MacQuarie University 137.111.162.20 - 1/20/2020 12:15:35 AM
Scars and Keloids
265
Dermatológica 1990;181:264-265
Is There a Link between Dendrocytes, Fibrosis and Sclerosis? G.E. Piérard, ./. Arrese-Estrada, C. Piérard-Franchimont, F. Deleixhe-Mauhin Department of Dermatopathology. CHU du San Tilman. Liège, Belgium
Key Words. Fibrosis • Sclerosis ■Dendrocyte • Factor XII la • Scleroderma • Dermatofibroma • Scar • Keloid Abstract. In a series of fibrotie and sclerotic diseases including scars, keloids, fibromas, scleroderma and lichen sclerosuset atrophicus. we found modifications in the dendrocyte population. Dendrocytes were numerous in fibrotie dis eases associated with little deposits of collagen. Conversely, they were almost absent in sclerotic diseases when the laydown of collagen was prominent. We hypothesize that dendrocytes, by their content in factor XII la, may limit the accu mulation of collagen in the skin.
Scleroderma and Lichen sclerosus et atrophicus Scleroderma and lichen sclerosus et atrophicus are two sclerotic diseases, because the dermal cell density is decreased compared to normal skin [9]. Acrosclerodcrma is a diffuse process while lichen sclerosus et atrophicus and morphea are two disorders, respectively, limited to the superficial dermis and to circumscribed parts of the integument. In early acroscleroderma, and at the periphery of mor phea and lichen sclerosus et atrophicus, we found numer ous large dendrocytes [3, 6]. When deposits of collagen were evidenced in these diseases, dendrocytes were almost totally absent. Scleroderma is currently considered as a disease of the microvasculature [10]. If dendrocytes may be considered as cells of the microvasculature [6], their disappearance in scleroderma could reflect the primary vascular alterations. It has been reported that factor XIII may be an effec tive treatment for scleroderma [11, 12]. Recent reports have also shown that factor XII la inhibits the in vitro syn thesis of collagen by fibroblasts of normal skin and scler oderma [ 13, 14]. It is therefore possible that the cause of cutaneous sclerosis in scleroderma is linked to the defi ciency in factor-XIIIa-positivc dendrocytes.
Downloaded by: MacQuarie University 137.111.162.20 - 1/20/2020 12:15:35 AM
Accurate morphologic observations usually precede and lay the foundation for studies aimed at determining pathogenesis. It is now possible to revisit the concept of fibrosis and sclerosis and to throw light on the influence of dendrocytes in these diseases. Fibrosis in reparative lesions is defined by the accumu lation of resident connective tissue cells, often associated with newly formed vessels. Normal collagen bundles are replaced by fibrillary collagen. Conversely, sclerosis is defined by the presence of thickened, homogeneous collagen bundles with little cells and vessels interspersed between them. In the past, all spindle-shaped cells of the dermis were called fibroblasts or fibrocytes. Recently dendrocytes have been identified among them. They contain factor XHIa [1-7], and many of them are associated with the dermal microvasculature [6, 7J. These cells have phago cytic properties and could be involved in immunological functions [5,8]. Could they also be involved in the regula tion of collagen synthesis and degradation? We raise the hypothesis that there is an inverse rela tionship between the density of dendrocytes and the amount of collagen deposits. Examples of such a relation ship primarily concern scleroderma, lichen sclcrosus et atrophicus, scars, keloids and dermatofibromas.
Is There a Link between Dendrocytes, Fibrosis and Sclerosis?
Dendrocytes arc numerous in early scarring [3, 7] and in scars of longer duration when deposits of collagen arc poor [3]. Conversely, scars with a well-developed extracellular matrix and keloids are devoid of dendro cytes. It is known that Black people have a tendency to form keloids very easily. We have observed that the normal skin of Black people contains a lower number of dendro cytes than that of Caucasians. We have also observed that in White people dendrocytes arc more numer ous in the superficial dermis than in the deep dermis and arc also more numerous in sun-exposed areas than in sun-protected areas [8]. Photochemotherapy also in duces an accumulation of dendrocytes when photosclero sis is absent [15]. If these observations may be linked, we could consider that the amount of light reaching the dermis could modulate the number of dendrocytes. Furthermore, the natural tendency of Black people to develop keloids could be related to their relative dendrocyte deficiency related to the photoprotection by melanin.
Dermatofibromas Dermatofibromas basically represent fibrotic lesions. In rare instances, however, sclerosis may be found at the center of the lesions. Dendrocytes and endothelial cells represent the two main cell populations of ‘fibrotic dermatofibromas' [3, 4, 16]. Protein synthesis, in particular of collagen, is then poor in the dendrocytes [16]. In ‘sclerotic dermatofibro mas’, we have not identified dendrocytes in the sclerotic foci, and they were only confined to the periphery of the lesions.
Hypothesis It is striking that our observations of fibrotic and scle rotic diseases lead to the same findings without any excep tion. Fibrosis is a dendrocyte-rich condition, while sclero sis is a dendrocyte-poor condition. As several cell func tions are modulated by factor XIII, we frame as an hypothesis that dendrocytes, by their content in factor XHIa, may contribute to a limitation in the laydown of collagen in the dermis.
References 1 Ccrio R. Spaull JR. Wilson Jones E: Identification of factor XII la in cutaneous tissue. Histopathology 1988;13:362-363. 2 Nemeth AJ. Pcnneys JR. Bernstein I IB : Fibrous papule: A tumor of the fibrohistiocytic cells that contain factor XHIa. J Am Acad Dermatol 1988;19:1102-1106. 3 Arrese Estrada J. Laso Dosai F. Piérard-Franchimont C. Piérard GE: Heterogeneity in the cell population of the dermis; in Piérard GE. Piérard-Franchimont C (eds): The Dermis - Front Biology to Diseases. Liege. Publ Monographies Dermatopathologiques Lié geoises, 1989. pp 1-12. 4 Cerio R. Spaull JR. Wilson Jones E: Histiocytoma cutis: A tumour of dermal dendrocytes (dermal dendrocytoma). Br J Dermatol 1989:120:197-206. 5 Cerio R. Griffiths CEM. Cooper KD. Nickoloff BJ. Hcadington JT: Characterization of factor XII la positive dermal dendritic cells in normal and inflamed skin. Br J Dermatol 1989:121:421^131. 6 Arrese Estrada J. Piérard GE: Factor-XIIIa-positive dendrocytes and the dermal microvascular unit. Dermatológica 1990:180: 51-53. 7 PenneysNS: Factor XIII expression in the skin: Observationsand a hypothesis. J Am Acad Dermatol 1990:22:484-488. 8 Piérard-Franchimont C, Arrese Estrada J. Piérard GE: Dendro cytes. cellules de Langerhans et photovieillissement. Ann Dermatol Vénéréol. in press. 9 Piérard GE: I listo logical and rheological grading of cutaneous scle rosis in scleroderma. Dermatológica 1989; 179:18—20. 10 Leroy EC: The vascular defect in scleroderma (systemic sclerosis). Acta Med Scand 1987;S715:165-168. 11 Thivolct J. Perot H. McunicrF. Bouchet B: Action thérapeutique du facteur FXIII de la coagulation dans la sclérodermie. Nouv Presse Méd 1975:4:2779-2781. 12 Guillevin L. Euler-Ziegler L.Chouvet B. et al: Treatment with fac tor XI 11and long-term follow-upof 86 patients with progressive sys temic sclerosis. Presse Méd 1985:14:2327-2330. 13 Paye M, Nusgens BV, Lapièrc ChM: Factor XIII of blood coagula tion modulates collagen biosynthesis by fibroblasts in vitro. Hae mostasis 1989:19:274-283. 14 Paye M. Read D. Nusgens B. Lapièrc ChM: Factor XIII in scler oderma: In vitro studies. Br J Dermatol 1990:122:371-382. 15 Piérard-Franchimont C, Nickcls-Read D. Ben Mosbah T. Arrese Estrada J. Piérard GE: Early dermatopathological signs related to bath PUVA therapy. J Pathol, in press. 16 Piérard GE. Piérard-Franchimont C. Van Cauwenberge D. Mélotte P. Christophe J. Lapièrc ChM: Histiocytofibromc et fibromatose palmaire de Dupuytren. Etude autohistoradiographique comparative de leurs activités prolifératives et biosynthétiques. Ann Dermatol Vénéréol 1985;112:877-881.
Received: April 23. 1990 Accepted: April 28. 1990 Dr. G.E. Piérard D epartm ent of D erm atopathology
CHU du Sart Tilman B-4000 Liège (Belgium)
Downloaded by: MacQuarie University 137.111.162.20 - 1/20/2020 12:15:35 AM
Scars and Keloids
265
