Esclerodermia: Hechos y teorías acerca de su patogénesis
Palabras clave:
escleroderma, esclerosis, patogénesis de esclerosisResumen
La esclerodermia es una de las enfermedades del tejido conectivo sobre cuyos mecanismos patogénicos existe mayor desconocimiento. Debido a que su característica fundamental es la fibrosis de la piel con compromiso interno o sin él, las investigaciones recientes tienden a explicar la fibrosis, y los resultados de numerosos estudios nos inducen a pensar que es una enfermedad heterogénea, en donde se conjugan anormalidades en el sistema inmune, en el endotelio, en el fibroblasto y en los componentes de la matriz extracelular. Este artículo pretende revisar algunas de las teorías más relevantes para el entendimiento de la patogénesis de la enfermedad, pasando por la teoría vascular, el papel de las citoquinas y los factores de crecimiento, hasta la teoría del microquimerismo como un factor de riesgo para desarrollar esclerodermia.
Biografía del autor/a
Lucya García Rodríguez, Universidad del Valle
Dermatóloga Docente, Universidad del Valle, Dermatología Hospital Universitario del Valle, Cali, Colombia
Referencias bibliográficas
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https://doi.org/10.1023/A:1020551610319
3. Kissin EY, Korn JH. Fibrosis in scleroderma. Rheum Dis Clin of North Am. 2003; 29(2): 351-69.
https://doi.org/10.1016/S0889-857X(03)00018-8
4. Navratil JS. Apoptosis and immune responses to self. Rheum Dis Clin North Am 2004; 30(1 ): 193-212.
https://doi.org/10.1016/S0889-857X(03)00110-8
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https://doi.org/10.1097/00002281-200211000-00009
6. Clark RA. Cutaneous tissue repair: basic biologic con- siderations. J Am Acad Dermatol 1985, 13:701-25.
https://doi.org/10.1016/S0190-9622(85)70213-7
7. LeRoy EC, Smith EA, Kahaleh MB, et al. A strategy for determining the pathogenesis of systemic sclerosis. Arthritis Rheum 1989, 32:817-25.
8. Border WA, Noble NA. Transforming growth factor-[beta] in tissue fibrosis. N Engl J Med. 1994;331: 1286-92.
https://doi.org/10.1056/NEJM199411103311907
9. lhn H, Yamane K, Kubo M, et al. Blockade of endoge- nous transforming growth factor [beta] signaling pre- vent upregulated collagen synthesis in scleroderma fi- broblasts: association with increased expression of transforming growth factor (beta] receptors. Arthritis Rheum. 2001; 44:474-80.
https://doi.org/10.1002/1529-0131(200102)44:2<474::AID-ANR67>3.0.CO;2-#
10. Kubo M, lhn H, Yamane K, et al. Upregulated expres- sion of transforming growth factor [beta] receptors in dermal fibroblasts in skin sections from patients with lo- calized scleroderma. Arthritis Rheum. 2001; 44:731-34.
https://doi.org/10.1002/1529-0131(200103)44:3<731::AID-ANR124>3.0.CO;2-U
11. Jelaska A, Korn JH. Role of apoptosis and transform-ing growth factor beta1 in fibroblast selection and acti-vation in systemic sclerosis. Arthritis Rheum. 2000; 43:2230-31.
https://doi.org/10.1002/1529-0131(200010)43:10<2230::AID-ANR10>3.0.CO;2-8
12. Hironobu l. Pathogenesis of fibrosis role of TGF beta and CTGF. Curr Op Rheumatol. 2002; 14(6), 681-85.
https://doi.org/10.1097/00002281-200211000-00009
13. Denton C P, Abraham O J. Transforming growth factor beta and connective tissue growth factor: key cytok- ines in scleroderma pathogenesis. Currt Op Rheuma- tol. 2001; 13(6):505-11.
https://doi.org/10.1097/00002281-200111000-00010
14. Mori Y, Chen, Shu-Jen, Varga J. Expression and regu- lation of intracellular SMAD signaling in scleroderma skin fibroblasts. Arthritis and rheumatism. 2003; 48(7):1964-78.
https://doi.org/10.1002/art.11157
15. Querfeld C, Eckes B, Huerkamp C,Krieg T, Solberg S. Expression of TGF-beta 1, -beta 2 and -beta 3 in local-ized and systemic scleroderma. J Dermatol Sci. 1999; 21 :13-22.
https://doi.org/10.1016/S0923-1811(99)00008-0
16. Dong C. Deficient Smad7 expression: a putative mo- lecular defect in scleroderma. Proc Natl Acad Sci USA. 2002; 99(6): 3908-13.
https://doi.org/10.1073/pnas.062010399
17. Restrepo JF. Expression of transforming growth factor-beta and platelet-derived growth factor in linear sclero- derma Biomedica. 2003; 23(4): 408-15.
18. Heldin C H, Miyazono K, Dijke P. TGF beta signalling from cell membrane to nucleus through SMAD proteins Nature 1997; 390(6659) 465-71.
https://doi.org/10.1038/37284
19. Fleischmajer R, Perlis JS, Krieg T, Timpl R. Variability in collagen and fibronectin synthesis by scleroderma. fibroblasts in primary culture. J lnvest Dermatol. 1981; 76: 400-3.
https://doi.org/10.1111/1523-1747.ep12520933
20. Takeda K. Decreased collagenase expression in scle- roderma J lnvest Dermatol. 1994; 103: 359-63.
https://doi.org/10.1111/1523-1747.ep12394936
21. Wallis DO. Abnormalities in fibrillin 1-containing mi- crofibrils in dermal fibroblast cultures from patients with systemic sclerosis (scleroderma). Arthritis Rheum 2001; 44(8): 1855-64.
https://doi.org/10.1002/1529-0131(200108)44:8<1855::AID-ART324>3.0.CO;2-Q
22. Brasington RO Jr. lmmunologic rheumatic disorders. J Allergy Clin lmmunol 2003; 111 (2 Suppl): S593-601.
https://doi.org/10.1067/mai.2003.79
23. Postlethwaite AE. Early immune events in scleroder- ma. Rheum.Dis. Clin. North Am. 1990; 16: 125-39.
24. Gruschwitz M, Peters KP, Heese A, Stosiek N, Kosh HU, Hornstein UP. Expression of adhesion proteins in- volved in cell-cell and cell-matrix interactions in the skin of patients with progressive systemic sclerosis. J Am Acad Dermatol. 1992; 27: 169-77.
https://doi.org/10.1016/0190-9622(92)70165-C
25. Chen K et al Epidemiology and patoghenesis of scle- roderma . Aust J Dermatol. 2003; 44 : 1-9.
26. Kissin EY. Fibrosis in scleroderma. Rheum Dis Clin North Am 2003; 29(2): 351-69.
https://doi.org/10.1016/S0889-857X(03)00018-8
27. Mouthon L, Seea, Shumack S. Pathogenie de la scle- rodermie systemique. Ann Med lnt Paris. 2002;153:67.
28. Gelber AC. Disease severity as a predictor of outcome in scleroderma. Lancet. 2002; 359(26): 277-79.
https://doi.org/10.1016/S0140-6736(02)07535-9
29. Artlett CM, Cox LA, Jimenez SA. Detection of cellular microchimerism of male or female origin in systemic sclerosis patients by polymerase chain reaction analy-sis of HLA-Cw antigens. Arthritis Rheum. 2000; 43:1062-7.
https://doi.org/10.1002/1529-0131(200005)43:5<1062::AID-ANR16>3.0.CO;2-P
30. Srivatsa B. Maternal cell microchimerism in newborn tissues. J Pediatr. 2003; 142(1 ): 31-5.
https://doi.org/10.1067/mpd.2003.mpd0327
31. Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Smith A, et al. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. Lancet. 1998;351 :559-62.
https://doi.org/10.1016/S0140-6736(97)08357-8
32. Nelson JL. Microchimerism in the pathogenesis of sys-temic sclerosis. Curr Opin Rheumatol. 1998, 10:564-71.
https://doi.org/10.1097/00002281-199811000-00010
2. Gavanescu O, Vazquez-Abad J, Mccauley J.L, Sene- cal, Doxsey S. Centrosome Proteins: A major class of autoantigens in Scleroderma. J Clinical lnmunology. 1999; (19) 3: 166-71.
https://doi.org/10.1023/A:1020551610319
3. Kissin EY, Korn JH. Fibrosis in scleroderma. Rheum Dis Clin of North Am. 2003; 29(2): 351-69.
https://doi.org/10.1016/S0889-857X(03)00018-8
4. Navratil JS. Apoptosis and immune responses to self. Rheum Dis Clin North Am 2004; 30(1 ): 193-212.
https://doi.org/10.1016/S0889-857X(03)00110-8
5. lhn H. Pathogenesis of fibrosis: role of TGF-[beta] and CTGF. Current Opinion in Rheumatology. 2002; 14(6):681-85.
https://doi.org/10.1097/00002281-200211000-00009
6. Clark RA. Cutaneous tissue repair: basic biologic con- siderations. J Am Acad Dermatol 1985, 13:701-25.
https://doi.org/10.1016/S0190-9622(85)70213-7
7. LeRoy EC, Smith EA, Kahaleh MB, et al. A strategy for determining the pathogenesis of systemic sclerosis. Arthritis Rheum 1989, 32:817-25.
8. Border WA, Noble NA. Transforming growth factor-[beta] in tissue fibrosis. N Engl J Med. 1994;331: 1286-92.
https://doi.org/10.1056/NEJM199411103311907
9. lhn H, Yamane K, Kubo M, et al. Blockade of endoge- nous transforming growth factor [beta] signaling pre- vent upregulated collagen synthesis in scleroderma fi- broblasts: association with increased expression of transforming growth factor (beta] receptors. Arthritis Rheum. 2001; 44:474-80.
https://doi.org/10.1002/1529-0131(200102)44:2<474::AID-ANR67>3.0.CO;2-#
10. Kubo M, lhn H, Yamane K, et al. Upregulated expres- sion of transforming growth factor [beta] receptors in dermal fibroblasts in skin sections from patients with lo- calized scleroderma. Arthritis Rheum. 2001; 44:731-34.
https://doi.org/10.1002/1529-0131(200103)44:3<731::AID-ANR124>3.0.CO;2-U
11. Jelaska A, Korn JH. Role of apoptosis and transform-ing growth factor beta1 in fibroblast selection and acti-vation in systemic sclerosis. Arthritis Rheum. 2000; 43:2230-31.
https://doi.org/10.1002/1529-0131(200010)43:10<2230::AID-ANR10>3.0.CO;2-8
12. Hironobu l. Pathogenesis of fibrosis role of TGF beta and CTGF. Curr Op Rheumatol. 2002; 14(6), 681-85.
https://doi.org/10.1097/00002281-200211000-00009
13. Denton C P, Abraham O J. Transforming growth factor beta and connective tissue growth factor: key cytok- ines in scleroderma pathogenesis. Currt Op Rheuma- tol. 2001; 13(6):505-11.
https://doi.org/10.1097/00002281-200111000-00010
14. Mori Y, Chen, Shu-Jen, Varga J. Expression and regu- lation of intracellular SMAD signaling in scleroderma skin fibroblasts. Arthritis and rheumatism. 2003; 48(7):1964-78.
https://doi.org/10.1002/art.11157
15. Querfeld C, Eckes B, Huerkamp C,Krieg T, Solberg S. Expression of TGF-beta 1, -beta 2 and -beta 3 in local-ized and systemic scleroderma. J Dermatol Sci. 1999; 21 :13-22.
https://doi.org/10.1016/S0923-1811(99)00008-0
16. Dong C. Deficient Smad7 expression: a putative mo- lecular defect in scleroderma. Proc Natl Acad Sci USA. 2002; 99(6): 3908-13.
https://doi.org/10.1073/pnas.062010399
17. Restrepo JF. Expression of transforming growth factor-beta and platelet-derived growth factor in linear sclero- derma Biomedica. 2003; 23(4): 408-15.
18. Heldin C H, Miyazono K, Dijke P. TGF beta signalling from cell membrane to nucleus through SMAD proteins Nature 1997; 390(6659) 465-71.
https://doi.org/10.1038/37284
19. Fleischmajer R, Perlis JS, Krieg T, Timpl R. Variability in collagen and fibronectin synthesis by scleroderma. fibroblasts in primary culture. J lnvest Dermatol. 1981; 76: 400-3.
https://doi.org/10.1111/1523-1747.ep12520933
20. Takeda K. Decreased collagenase expression in scle- roderma J lnvest Dermatol. 1994; 103: 359-63.
https://doi.org/10.1111/1523-1747.ep12394936
21. Wallis DO. Abnormalities in fibrillin 1-containing mi- crofibrils in dermal fibroblast cultures from patients with systemic sclerosis (scleroderma). Arthritis Rheum 2001; 44(8): 1855-64.
https://doi.org/10.1002/1529-0131(200108)44:8<1855::AID-ART324>3.0.CO;2-Q
22. Brasington RO Jr. lmmunologic rheumatic disorders. J Allergy Clin lmmunol 2003; 111 (2 Suppl): S593-601.
https://doi.org/10.1067/mai.2003.79
23. Postlethwaite AE. Early immune events in scleroder- ma. Rheum.Dis. Clin. North Am. 1990; 16: 125-39.
24. Gruschwitz M, Peters KP, Heese A, Stosiek N, Kosh HU, Hornstein UP. Expression of adhesion proteins in- volved in cell-cell and cell-matrix interactions in the skin of patients with progressive systemic sclerosis. J Am Acad Dermatol. 1992; 27: 169-77.
https://doi.org/10.1016/0190-9622(92)70165-C
25. Chen K et al Epidemiology and patoghenesis of scle- roderma . Aust J Dermatol. 2003; 44 : 1-9.
26. Kissin EY. Fibrosis in scleroderma. Rheum Dis Clin North Am 2003; 29(2): 351-69.
https://doi.org/10.1016/S0889-857X(03)00018-8
27. Mouthon L, Seea, Shumack S. Pathogenie de la scle- rodermie systemique. Ann Med lnt Paris. 2002;153:67.
28. Gelber AC. Disease severity as a predictor of outcome in scleroderma. Lancet. 2002; 359(26): 277-79.
https://doi.org/10.1016/S0140-6736(02)07535-9
29. Artlett CM, Cox LA, Jimenez SA. Detection of cellular microchimerism of male or female origin in systemic sclerosis patients by polymerase chain reaction analy-sis of HLA-Cw antigens. Arthritis Rheum. 2000; 43:1062-7.
https://doi.org/10.1002/1529-0131(200005)43:5<1062::AID-ANR16>3.0.CO;2-P
30. Srivatsa B. Maternal cell microchimerism in newborn tissues. J Pediatr. 2003; 142(1 ): 31-5.
https://doi.org/10.1067/mpd.2003.mpd0327
31. Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Smith A, et al. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. Lancet. 1998;351 :559-62.
https://doi.org/10.1016/S0140-6736(97)08357-8
32. Nelson JL. Microchimerism in the pathogenesis of sys-temic sclerosis. Curr Opin Rheumatol. 1998, 10:564-71.
https://doi.org/10.1097/00002281-199811000-00010
Cómo citar
1.
García Rodríguez L. Esclerodermia: Hechos y teorías acerca de su patogénesis. rev. asoc. colomb. dermatol. cir. dematol. [Internet]. 1 de octubre de 2004 [citado 18 de abril de 2024];12(3):37-42. Disponible en: https://revista.asocolderma.org.co/index.php/asocolderma/article/view/588
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2004-10-01
Cómo citar
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García Rodríguez L. Esclerodermia: Hechos y teorías acerca de su patogénesis. rev. asoc. colomb. dermatol. cir. dematol. [Internet]. 1 de octubre de 2004 [citado 18 de abril de 2024];12(3):37-42. Disponible en: https://revista.asocolderma.org.co/index.php/asocolderma/article/view/588
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