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Vol. 100. Núm. S2.
Mirando hacia el futuro en Dermatología Extraordinario del Centenario. Parte II
Páginas 75-83 (Diciembre 2009)
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Vol. 100. Núm. S2.
Mirando hacia el futuro en Dermatología Extraordinario del Centenario. Parte II
Páginas 75-83 (Diciembre 2009)
Acceso a texto completo
Keloid Scarring: New Treatments Ahead
Queloides: nuevos tratamientos en el futuro
Visitas
5293
Ulrich Mrowietza,
Autor para correspondencia
umrowietz@dermatology.uni-kiel.de

Correspondence: Department of Dermatology. University Medical Center Schleswig-Holstein, Campus Kiel. Schittenhelmstr. 7. 24105 Kiel. Germany.
, Oliver Seifertb
a Department of Dermatology. University Medical Center Schleswig-Holstein. Campus Kiel. Kiel. Germany
b Department of Dermatology. County Hospital Ryhov. Jönköping. Sweden
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Abstract

Keloid disease presents a healthcare challenge: patients suffer from pruritus, pain, inflammation, and cosmetic disfigurement. There is no single effective therapeutic regimen for keloids. Numerous treatment options have been described including occlusive dressings, compression therapy, intralesional steroid injections, laser and radiation therapy, cryosurgery, 5-fluorouracil, interferon, and imiquimod cream, but managing keloid disease still is a considerable problem for clinicians. Better understanding of the molecular mechanisms behind keloid disease led to the development of new promising therapies like the application of recombinant TGF-β3, interleukin 10, and imatinib mesylate.

This review provides an overview of the existing therapeutic options for keloid disease and summarizes upcoming future therapies with a special focus on blocking the transforming growth factor-beta pathway.

Key words:
keloid
treatment
physiopathology
molecular mechanisms
TGF-β3
interleukin 10
imatinib mesylate
Resumen

Los queloides representan un reto de atención sanitaria: los pacientes padecen prurito, dolor, inflamación y desfiguración cosmética. No existe ningún tratamiento efectivo para los queloides. Se han descrito numerosas opciones terapéuticas que incluyen vendajes oclusivos, terapia de compresión, corticoides intralesionales, láser, radioterapia, criocirugía, 5-fluorouracilo, interferón e imiquimod, pero el tratamiento continúa siendo un problema considerable para los clínicos.

Se han desarrollado nuevas y prometedoras terapias, como la aplicación de TGF-β3 recombinante, interleuquina 10 y mesilato de imatinib gracias a un mayor conocimiento de los mecanismos moleculares responsables de los queloides.

Esta revisión ofrece una visión de conjunto de las opciones terapéuticas disponibles para los queloides y resume las futuras terapias, haciendo especial énfasis en los bloqueadores de la vía del factor de crecimiento transformador beta.

Palabras clave:
queloides
tratamiento
fisiopatología
mecanismos moleculares
TGF-β3
interleuquina 10
mesilato de imatinib
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References
[1.]
D. Ladin.
The art and science of wound care.
Plast Reconstr Surg, 96 (1995), pp. 748
[2.]
J.H. Breasted.
The Edwin Smith surgical papyrus.
Hieroglyphic translation and commentary, University of Chicago Press, (1930),
[3.]
J.L.M. Alibert.
Description des maladies de la peau observées a l’hôpital Saint-Louis et exposition des meilleures methodes suives pour leur traitment.
Barrois l’aine et fils, (1806),
[4.]
T.L. Tuan, L.S. Nichter.
The molecular basis of keloid and hypertrophic scar formation.
Mol Med Today, 4 (1998), pp. 19-24
[5.]
E.E. Tredget, B. Nedelec, P.G. Scott, A. Ghahary.
Hypertrophic scars, keloids, and contractures. The cellular and molecular basis for therapy.
Surg Clin North Am, 77 (1997), pp. 701-730
[6.]
P. Pitche.
What is true in “spontaneous” keloids?.
Ann Dermatol Venereol, 133 (2006), pp. 501
[7.]
D.A. McGrouther.
Hypertrophic or keloid scars?.
Eye, 8 (1994), pp. 200-203
[8.]
A. Bayat, G. Arscott, W.E. Ollier, M.W. Ferguson, D.A. Mc Grouther.
Description of site-specific morphology of keloid phenotypes in an Afrocaribbean population.
Br J Plast Surg, 57 (2004), pp. 122-133
[9.]
A.S. Prado, M. Fontbona.
A 1.8-kg keloid of the arm.
Plast Reconstr Surg, 117 (2006), pp. 335-336
[10.]
A.E. Brissett, D.A. Sherris.
Scar contractures, hypertrophic scars, and keloids.
Facial Plast Surg, 17 (2001), pp. 263-272
[11.]
W.H. Lindsey, P.T. Davis.
Facial keloids. A 15-year experience.
Arch Otolaryngol Head Neck Surg, 123 (1997), pp. 397-400
[12.]
B. Cosman, F. Crikelair, M.C. Ju, J.C. Gaulin, R. Lattes.
The surgical treatment of keloids.
Plast Reconstr Surg, 27 (1961), pp. 335-345
[13.]
H.P. Schierle, D. Scholz, G. Lemperle.
Elevated levels of testosterone receptors in keloid tissue: an experimental investigation.
Plast Reconstr Surg, 100 (1997), pp. 390-395
[14.]
J.O. Oluwasanmi.
Keloids in the African.
Clin Plast Surg, 1 (1974), pp. 179-195
[15.]
D. Bloom.
Heredity of keloids.
N Y State Med J, 56 (1956), pp. 511-519
[16.]
O. Bock, G. Schmid-Ott, P. Malewski, U. Mrowietz.
Quality of life of patients with keloid and hypertrophic scarring.
Arch Dermatol Res, 297 (2006), pp. 433-438
[17.]
T.A. Mustoe, R.D. Cooter, M.H. Gold, F.D. Hobbs, A.A. Ramelet, P.G. Shakespeare, et al.
International clinical recommendations on scar management.
Plast Reconstr Surg, 110 (2002), pp. 560-571
[18.]
M.R. Schaffer, P.A. Efron, F.J. Thornton, K. Klingel, S.S. Gross, A. Barbul.
Nitric oxide, an autocrine regulator of wound fibroblast synthetic function.
J Immunol, 158 (1997), pp. 2375-2381
[19.]
Y.C. Kauh, S. Rouda, G. Mondragon, R. Tokarek, M. diLeonardo, R.S. Tuan, et al.
Major suppression of pro-alpha1(I) type I collagen gene expression in the dermis after keloid excision and immediate intrawound injection of triamcinolone acetonide.
J Am Acad Dermatol, 37 (1997), pp. 586-589
[20.]
M. Jalali, A. Bayat.
Current use of steroids in management of abnormal raised skin scars.
Surgeon, 5 (2007), pp. 175-180
[21.]
M.A. Darzi, N.A. Chowdri, S.K. Kaul, M. Khan.
Evaluation of various methods of treating keloids and hypertrophic scars: a 10-year follow-up study.
Br J Plast Surg, 45 (1992), pp. 374-379
[22.]
A.M. Layton, J. Yip, W.J. Cunliffe.
A comparison of intralesional triamcinolone and cryosurgery in the treatment of acne keloids.
Br J Dermatol, 130 (1994), pp. 498-501
[23.]
G. Yosipovitch, M. Widijanti Sugeng, A. Goon, Y.H. Chan, C.L. Goh.
A comparison of the combined effect of cryotherapy and corticosteroid injections versus corticosteroids and cryotherapy alone on keloids: a controlled study.
J Dermatolog Treat, 12 (2001), pp. 87-90
[24.]
W. Manuskiatti, R.E. Fitzpatrick.
Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped pulsed-dye laser treatments.
Arch Dermatol, 138 (2002), pp. 1149-1155
[25.]
P. Durani, A. Bayat.
Levels of evidence for the treatment of keloid disease.
J Plast Reconstr Aesthet Surg, 61 (2008), pp. 4-17
[26.]
T.A. Mustoe.
Evolution of silicone therapy and mechanism of action in scar management.
Aesthetic Plast Surg, 32 (2008), pp. 82-92
[27.]
B. Berman, O.A. Pérez, S. Konda, B.E. Kohut, M.H. Viera, S. Delgado, et al.
A review of the biologic effects, clinical efficacy, and safety of silicone elastomer sheeting for hypertrophic and keloid scar treatment and management.
Dermatol Surg, 33 (2007), pp. 1291-1302
[28.]
L. O’Brien, A. Pandit.
Silicon gel sheeting for preventing and treating hypertrophic and keloid scars.
Cochrane Database Syst Rev, (2006),
[29.]
F.B. Niessen, P.H. Spauwen, J. Schalkwijk, M. Kon.
On the nature of hypertrophic scars and keloids: a review.
Plast Reconstr Surg, 104 (1999), pp. 1435-1458
[30.]
K. Ernst, M. Hundeiker.
Results of cryosurgery in 394 pa tients with hypertrophic scars and keloids.
Hautarzt, 46 (1995), pp. 462-466
[31.]
J.P. Shepherd, R.P. Dawber.
The response of keloid scars to cryosurgery.
Plast Reconstr Surg, 70 (1982), pp. 677-682
[32.]
T.S. Alster, C.M. Williams.
Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye laser.
Lancet, 345 (1995), pp. 1198-1200
[33.]
C. Dierickx, M.P. Goldman, R.E. Fitzpatrick.
Laser treatment of erythematous/hypertrophic and pigmented scars in 26 patients.
Plast Reconstr Surg, 95 (1995), pp. 84-90
[34.]
K. Kumar, B.S. Kapoor, P. Rai, H.S. Shukla.
In-situ irradiation of keloid scars with Nd:YAG laser.
J Wound Care, 9 (2000), pp. 213-215
[35.]
G.R. Kantor, R.G. Wheeland, P.L. Bailin, N.P. Walker, J.L. Ratz.
Treatment of earlobe keloids with carbon dioxide laser excision: a report of 16 cases.
J Dermatol Surg Oncol, 11 (1985), pp. 1063-1067
[36.]
D.I. Klumpar, J.C. Murray, M. Anscher.
Keloids treated with excision followed by radiation therapy.
J Am Acad Dermatol, 31 (1994), pp. 225-231
[37.]
R. Ogawa, K. Mitsuhashi, H. Hyakusoku, T. Miyashita.
Postoperative electron-beam irradiation therapy for keloids and hypertrophic scars: retrospective study of 147 cases followed for more than 18 months.
Plast Reconstr Surg, 111 (2003), pp. 547-553
[38.]
R. Ragoowansi, P.G. Cornes, A.L. Moss, J.P. Glees.
Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy.
Plast Reconstr Surg, 111 (2003), pp. 1853-1859
[39.]
R.G. Panizzon.
Dermatologic radiotherapy.
Hautarzt, 58 (2007), pp. 701-710
[40.]
A.P. Sclafani, L. Gordon, M. Chadha, T. Romo 3rd.
Prevention of earlobe keloid recurrence with postoperative corticosteroid injections versus radiation therapy: a randomized, prospective study and review of the literature.
Dermatol Surg, 22 (1996), pp. 569-574
[41.]
M. Maarouf, U. Schleicher, A. Schmachtenberg, J. Ammon.
Radiotherapy in the management of keloids. Clinical experience with electron beam irradiation and comparison with X-ray therapy.
Strahlenther Onkol, 178 (2002), pp. 330-335
[42.]
M. Caccialanza, R. Piccinno, A. Schiera.
Postoperative radiotherapy of keloids: a twenty-year experience.
Eur J Dermatol, 12 (2002), pp. 58-62
[43.]
I.B. Fraunholz, A. Gerstenhauer, H.D. Bottcher.
Results of postoperative (90)Sr radiotherapy of keloids in view of patients’ subjective assessment.
Strahlenther Onkol, 181 (2005), pp. 724-729
[44.]
B. Guix, I. Henríquez, A. Andrés, F. Finestres, J.I. Tello, A. Martínez.
Treatment of keloids by high-dose-rate brachytherapy: A seven-year study.
Int J Radiat Oncol Biol Phys, 50 (2001), pp. 167-172
[45.]
J.J. Kovalic, C.A. Pérez.
Radiation therapy following keloidectomy: a 20-year experience.
Int J Radiat Oncol Biol Phys, 17 (1989), pp. 77-80
[46.]
J.F. Doornbos, T.J. Stoffel, A.C. Hass, D.H. Hussey, A.P. Vigliotti, B.C. Wen, et al.
The role of kilovoltage irradiation in the treatment of keloids.
Int J Radiat Oncol Biol Phys, 18 (1990), pp. 833-839
[47.]
B. Brent.
The role of pressure therapy in management of earlobe keloids: preliminary report of a controlled study.
Ann Plast Surg, 1 (1978), pp. 579-581
[48.]
G.E. Rauscher, W.L. Kolmer.
Treatment of recurrent earlobe keloids.
Cutis, 37 (1986), pp. 67-68
[49.]
B. Berman, J. Kaufman.
Pilot study of the effect of postoperative imiquimod 5% cream on the recurrence rate of excised keloids.
J Am Acad Dermatol, 47 (2002), pp. S209-S211
[50.]
R.F. Martín-García, A.C. Busquets.
Postsurgical use of imiquimod 5% cream in the prevention of earlobe keloid recurrences: results of an open-label, pilot study.
Dermatol Surg, 31 (2005), pp. 1394-1398
[51.]
P.J. Patel, R.B. Skinner Jr.
Experience with keloids after excision and application of 5% imiquimod cream.
[52.]
F.M. Cacao, V. Tanaka, M.C. Messina.
Failure of imiquimod 5% cream to prevent recurrence of surgically excised trunk keloids.
Dermatol Surg, 35 (2009), pp. 629-633
[53.]
M. Blumenkranz, E. Hernández, A. Ophir, E.W. Norton.
5-fluorouracil: new applications in complicated retinal detachment for an established antimetabolite.
Ophthalmology, 91 (1984), pp. 122-130
[54.]
J.W. de Waard, B.M. de Man, T. Wobbes, C.J. van der Linden, T. Hendriks.
Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5-fluorouracil.
Eur J Cancer, 34 (1998), pp. 162-167
[55.]
S.A. Jiménez, B. Freundlich, J. Rosenbloom.
Selective inhibition of human diploid fibroblast collagen synthesis by interferons.
J Clin Invest, 74 (1984), pp. 1112-1116
[56.]
B. Berman, M.R. Duncan.
Short-term keloid treatment in vivo with human interferon alfa-2b results in a selective and persistent normalization of keloidal fibroblast collagen, glycosaminoglycan, and collagenase production in vitro.
J Am Acad Dermatol, 21 (1989), pp. 694-702
[57.]
M.M. al-Khawajah.
Failure of interferon-alpha 2b in the treatment of mature keloids.
Int J Dermatol, 35 (1996), pp. 515-517
[58.]
W.F. Larrabee Jr., C.A. East, H.S. Jaffe, C. Stephenson, K.E. Peterson.
Intralesional interferon gamma treatment for keloids and hypertrophic scars.
Arch Otolaryngol Head Neck Surg, 116 (1990), pp. 1159-1162
[59.]
E. Copcu, N. Sivrioglu, Y. Oztan.
Combination of surgery and intralesional verapamil injection in the treatment of the keloid.
J Burn Care Rehabil, 25 (2004), pp. 1-7
[60.]
J. Rehman, A. Benet, A. Melman.
Use of intralesional verapamil to dissolve Peyronie's disease plaque: a long-term single-blind study.
Urology, 51 (1998), pp. 620-626
[61.]
J. Varga, D. Abraham.
Systemic sclerosis: a prototypic multisystem fibrotic disorder.
J Clin Invest, 117 (2007), pp. 557-567
[62.]
G.C. Blobe, W.P. Schiemann, H.F. Lodish.
Role of transforming growth factor beta in human disease.
N Engl J Med, 342 (2000), pp. 1350-1358
[63.]
M. Shah, D.M. Foreman, M.W. Ferguson.
Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta.
Lancet, 339 (1992), pp. 213-214
[64.]
C.P. Denton, P.A. Merkel, D.E. Furst, D. Khanna, P. Emery, V.M. Hsu, et al.
Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192.
Arthritis Rheum, 56 (2007), pp. 323-333
[65.]
A.L. Mead, T.T. Wong, M.F. Cordeiro, I.K. Anderson, P.T. Khaw.
Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery.
Invest Ophthalmol Vis Sci, 44 (2003), pp. 3394-3401
[66.]
M. Gary-Bobo, P. Nirde, A. Jeanjean, A. Morere, M. García.
Mannose 6-phosphate receptor targeting and its applications in human diseases.
Curr Med Chem, 14 (2007), pp. 2945-2953
[67.]
B. Santiago, I. Gutiérrez-Canas, J. Dotor, G. Palao, J.J. Lasarte, J. Ruiz, et al.
Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis.
J Invest Dermatol, 125 (2005), pp. 450-455
[68.]
J.S. Munger, X. Huang, H. Kawakatsu, M.J. Griffiths, S.L. Dalton, J. Wu, et al.
The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis.
Cell, 96 (1999), pp. 319-328
[69.]
G.S. Horan, S. Wood, V. Ona, D.J. Li, M.E. Lukashev, P.H. Weinreb, et al.
Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation.
Am J Respir Crit Care Med, 177 (2008), pp. 56-65
[70.]
K. Puthawala, N. Hadjiangelis, S.C. Jacoby, E. Bayongan, Z. Zhao, Z. Yang, et al.
Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis.
Am J Respir Crit Care Med, 177 (2008), pp. 82-90
[71.]
W. Ishida, Y. Mori, G. Lakos, L. Sun, F. Shan, S. Bowes, et al.
Intracellular TGF-beta receptor blockade abrogates Smad-dependent fibroblast activation in vitro and in vivo.
J Invest Dermatol, 126 (2006), pp. 1733-1744
[72.]
Y. Mori, W. Ishida, S. Bhattacharyya, Y. Li, L.C. Platanias, J. Varga.
Selective inhibition of activin receptor-like kinase 5 signaling blocks profibrotic transforming growth factor beta responses in skin fibroblasts.
Arthritis Rheum, 50 (2004), pp. 4008-4021
[73.]
D.S. Krause, R.A. Van Etten.
Tyrosine kinases as targets for cancer therapy.
N Engl J Med, 353 (2005), pp. 172-187
[74.]
J.H. Distler, A. Jungel, L.C. Huber, U. Schulze-Horsel, J. Zwerina, R.E. Gay, et al.
Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis.
Arthritis Rheum, 56 (2007), pp. 311-322
[75.]
O. Bock, H. Yu, S. Zitron, A. Bayat, M.W. Ferguson, U. Mrowietz.
Studies of transforming growth factors beta 1-3 and their receptors I and II in fibroblast of keloids and hypertrophic scars.
Acta Derm Venereol, 85 (2005), pp. 216-220
[76.]
M. Shah, D.M. Foreman, M.W. Ferguson.
Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring.
J Cell Sci, 108 (1995), pp. 985-1002
[77.]
M.W. Ferguson, J. Duncan, J. Bond, J. Bush, P. Durani, K. So, et al.
Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies.
Lancet, 373 (2009), pp. 1264-1274
[78.]
M. Ghazizadeh.
Essential role of IL-6 signaling pathway in keloid pathogenesis.
J Nippon Med Sch, 74 (2007), pp. 11-22
[79.]
K.W. Liechty, H.B. Kim, N.S. Adzick, T.M. Crombleholme.
Fetal wound repair results in scar formation in interleukin10-deficient mice in a syngeneic murine model of scarless fetal wound repair.
J Pediatr Surg, 35 (2000), pp. 866-872
[80.]
W.H. Peranteau, L. Zhang, N. Muvarak, A.T. Badillo, A. Radu, P.W. Zoltick, et al.
IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation.
J Invest Dermatol, 128 (2008), pp. 1852-1860
[81.]
G.Y. Zhang, C.G. Yi, X. Li, Y. Zheng, Z.G. Niu, W. Xia, et al.
Inhibition of vascular endothelial growth factor expression in keloid fibroblasts by vector-mediated vascular endothelial growth factor shRNA: a therapeutic potential strategy for keloid.
Arch Dermatol Res, 300 (2008), pp. 177-184
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