2536
Views & Citations1536
Likes & Shares
Keloid is
a benign fibrous growth, which presents in scar tissue of predisposed
individuals. Although the pathogenesis of keloid disease is not well
understood, it is considered to be the end product of an abnormal healing
process. However, it is possible that several factors such as age of onset,
sex, cause of scarring, blood groups, anatomical site, presence of family
history, number of injured sites (multiple/single) have an important role in
keloid formation. Keloids appear as firm, mildly tender, bosselated tumors with
a shiny surface. The main differential
diagnosis of keloid is hypertrophic scar. No single therapeutic modality is
best for all keloids, so prevention is the first rule in keloid. This study
gives a mini review of keloid formation, and this is the object of this study.
Keywords: Keloids, Pathogenesis, Risk factors,
Diagnosis, Different diagnosis, Histopathology, Treatment, Prevention
DEFINITION
Keloid is a
benign fibrous growth, presents in scar tissue of predisposed individuals,
extends beyond the borders of the original wound, doesn’t usually regress
spontaneously and tends to recur after excision. It is a result of irregular
wound healing following skin insults, but sometimes occurs spontaneously [1,2].
PATHOGENESIS
Pathogenesis
of keloid formation is not well cleared, but it is the end product of an
abnormal healing process [3]. Therefore, are several theories of keloid
formation according to induced factor. Some of them implicate certain cytokines
like Transforming growth factor beta (TGF-b) [4-6], vascular endothelial growth
factor (VEGF) [6], connective tissue growth factor (CTGF) [6] or
Platelet-derived growth factor (PDGF) [7]. Other implicates keratinocyte [8].
In contrast, some theories suggest that fibroblasts have the initial disorder
[3,9-11]. Recent evidence has indicated the role of type of immune response in
keloid formation, or maybe a role of mast cell [12].
EPIDEMIOLOGY AND ETIOLOGY (RISK FACTORS OF
KELOIDS)
Genetic predisposition
There is a clear genetic
component given the correlation with family history, which supported by the
following phenomena: (a) Some patients with keloids report a positive family
history [13,14]. (b) High occurrence in identical twins [14-16]. (c) Higher
predisposition in Blacks, Hispanics and Asians, less frequently in Caucasians
[15]. (d) Increased incidence of keloids in patients with some genetic syndromes
like Turner syndrome, Opitz-Kaveggia syndrome, Rubinstein Taybi syndrome and
Ehlers Danlos syndrome [17,18].
Blood groups
People with blood group A
have high probability to develop keloids compared with other blood groups [19].
Melanin
Anatomical site
Several studies indicated to
the role of anatomical site in keloid formation, which supported by the
following phenomena: (a) Genetically susceptible individuals form keloids after
wounding but not at every body site [15]. (b) Generally, keloids tend to occur
on highly mobile sites with high tension such as shoulders, neck and presternum
[21,22]. (c) There are familial patterns of keloid distribution [23].
Causes of keloids (type of skin injury)
Keloids may develop following any skin insult
like burn, trauma, surgery, piercings, acne, vaccinations [13], but not all
such insults lead to a keloid scar even in the susceptible individuals [15].
Age of onset: Although keloids could occur at any age, they are rare in first decade,
most likely to occur in second and third decades and tend to decrease in older
[15,16,19,20].
Sex: Incidence of keloids
is usually equal in females and males [16,24-26], but sometime there is higher
incidence in female [15,26] or in male [27].
Note: The above risk
factors are unmodifiable factors, but there are modifiable factors like delayed
healing [28] and hypertension [29].
DIAGNOSIS
Keloids appear as firm, mildly tender,
bosselated tumors with a shiny surface. In the Caucasian patient, keloids tend
to be erythematous and telangiectatic; they are often hyper pigmented in
darker-skinned individuals. Keloids are often pruritic and painful, in addition
to significant effects of patient’s quality of life, both physically and
psychologically, especially in excessive scarring [13].
DIFFERENTIAL DIAGNOSES
The main differential diagnosis of keloid is
hypertrophic scar. Hypertrophic scars, which defined as raised scars that
remained within the boundaries of the original lesion, often regressing
spontaneously after the initial injury and rarely recurring after surgical
excision. In contrast, a keloid scar is defined as a dermal lesion that spreads
beyond the margin of the original wound, continues to grow over time, does not
regress spontaneously and commonly recurring after excision [19].
TREATMENT
Standard treatments
These include occlusive dressings, compression
therapy and intralesional corticosteroid injections. Occlusive dressings
include silicone gel sheets and dressings, non-silicone occlusive sheets and
cordran tape [30-32]. Compression therapy involves pressure, which has long
been known to have thinning effects on skin. Reduction in the cohesiveness of
collagen fibers in pressure treated hypertrophic scars has been demonstrated by
electron microscopy [30,33]. Corticosteroids, specifically intralesional
corticosteroid injections, have been the mainstay of treatment [30].
Excision: Decreased recurrence
rates have been reported with excision in combination with other postoperative
modalities, such as radiotherapy, injected IFN or corticosteroid therapy [30].
Radiotherapy: Radiation destroys fibroblasts in the wound, prevents neovascularization,
which ultimately leads to a decreased production of collagen [28,34].
Laser therapy: Ablative lasers (Carbon dioxide (10,600 nm), Erbium: Yttrium aluminium
garnet laser (Er: YAG) (1064 nm), Argon 488 nm laser) and Non-ablative lasers
like Pulsed-dye laser (585 nm), because of its efficacy, safety, and relatively
low cost, the PDL remains the laser treatment of choice for keloids
hypertrophic scars [30].
Intralesional/topical apply of following drugs
IFN injections [26], 5-Fluorouracil [26],
Doxorubicin (Adriamycin) [30], Bleomycin [35], Verapamil [35], Retinoic acid [35],
Imiquimod 5% cream [35], Tamoxifen [35], Tacrolimus [35], Botulinum Toxin A [35].
Other promising therapies
The anti-angiogenic factors, including the
vascular endothelial growth factor (VEGF) inhibitors (e.g. Bevacizumab).
Phototherapy (photodynamic therapy - PDT), UVA-1 therapy, narrow band UVB
therapy. Tumor necrosis factor (TNF) alpha inhibitor (etanercept). Recombinant
human interleukin (rhIL-10) which are directed at decreasing collagen synthesis
[28].
Note: A previous study
found that 8% of keloids resolved spontaneously after 5 years [35].
PREVENTION
1.
Burrows NP, Lovell CR (2010) Rook textbook of
dermatology. Volume 3, 8th Edn.
2.
Burton CS, Escaravage V (2015) Bolognia text book. Volume
2, 2nd Edn.
3.
Shih B, Garside E, McGrouther DA, Bayat A (2010)
Molecular dissection of abnormal wound healing processes resulting in keloid
disease. Wound Repair Regen 18: 139-153.
4.
He S, Liu X, Yang Y, Huang W, Xu S, et al. (2010)
Mechanisms of transforming growth factor β1/Smad signalling mediated by
mitogen‐activated protein kinase pathways in keloid fibroblasts. Br J Dermatol
162: 538-546.
5.
Li J, Cao J, Li M, Yu Y, Yang Y, et al. (2011)
Collagen triple helix repeat containing‐1 inhibits transforming growth
factor‐β1‐induced collagen type I expression in keloid. Br J Dermatol 164:
1030-1036.
6.
Robles DT, Moore E, Draznin M, Berg D (2007)
Keloids: Pathophysiology and management. Dermatol Online J 13: 9.
7.
Hu ZC, Tang B, Guo D, Zhang J, Liang YY, et al.
(2014) Expression of insulin-like growth factor-1 receptor in keloid and
hypertrophic scar. Clin Exp Dermatol 39: 822-828.
8.
Hahn JM, Glaser K, McFarland KL, Aronow BJ, Boyce
ST, et al. (2013) Keloid‐derived keratinocytes exhibit an abnormal gene
expression profile consistent with a distinct causal role in keloid pathology.
Wound Repair Regen 21: 530-544.
9.
Russell SB, Russell JD, Trupin KM, Gayden AE,
Opalenik SR, et al. (2010) Epigenetically altered wound healing in keloid
fibroblasts. J Invest Dermatol 130: 2489-2496.
10.
Zulato E, Favaretto F, Veronese C, Campanaro S,
Marshall JD, et al. (2011) ALMS1-deficient fibroblasts over-express
extra-cellular matrix components, display cell cycle delay and are resistant to
apoptosis. PLoS One 6: e19081.
11.
De Felice B, Ciarmiello LF, Mondola P, Damiano S,
Seru R, et al. (2007) Differential p63 and p53 expression in human keloid
fibroblasts and hypertrophic scar fibroblasts. DNA Cell Biol 26: 541-547.
12.
Wulff BC, Parent AE, Meleski MA, DiPietro LA,
Schrementi ME, et al. (2010) Mast cells contribute to scar formation during
fetal wound healing. J Invest Dermatol 132: 458-465.
13.
Gauglitz GG, Korting HC, Pavicic T, Ruzicka T,
Jeschke MG (2011) Hypertrophic scarring and keloids: Pathomechanisms and
current and emerging treatment strategies. Mol Med 17: 113-125.
14.
Halim A, Emami A, Salahshourifar I, Kannan T (2012)
Keloid scarring: understanding the genetic basis, advances and prospects. Arch
Plast Surg 39: 184-189.
15.
Bayat A, Arscott G, Ollier WE, McGrouther DA,
Ferguson MW (2005) Keloid disease: Clinical relevance of single versus multiple
site scare. Br J Plast Surg 58: 28-37.
16.
Ramakrishnan KM, Thomas KP, Sundararajan CR (1964)
Study of 1,000 patients with keloids in South India. Plast Reconstr Surg 53:
276-280.
17.
Sun LM, Wang KH, Lee YC (2014) Keloid incidence in
Asian people and its comorbidity with other fibrosis-related diseases: A
nationwide population-based study. Arch Dermatol Res 306: 803-808.
18.
Shih B, Bayat A (2010) Genetics of keloid scarring.
Arch Dermatol Res 302: 319-339.
19.
Shaheen A, Khaddam J, Kesh F (2016) Risk factors of
keloids in Syrians. BMC Dermatol 16: 13.
20.
Gao FL, Jin R, Zhang L, Zhang YG (2013) The
contribution of melanocytes to pathological scar formation during wound
healing. Int J Clin Exp Med 6: 609-613.
21.
Naylor MC, Brissett AE (2012) Current concepts in
the etiology and treatment of keloids. Facial Plast Surg 28: 505-512.
22.
Ogawa R, Okai K, Tokumura F, Mori K, Ohmori Y, et
al. (2012) The relationship between skin stretching/contraction and pathologic
scarring: The important role of mechanical forces in keloid generation. Wound Repair
Regen 20: 149-157.
23.
Clark JA, Turner ML, Howard L, Stanescu H, Kleta R,
et al. (2009) Description of familial keloids in five pedigrees: Evidence for
autosomal dominant inheritance and phenotypic heterogeneity. BMC Dermatol 9: 8.
24.
Mouhari-Toure A, Saka B, Kombaté K, Akakpo S,
Egbohou P, et al. (2012) Is there an association between keloids and blood
groups? ISRN Dermatol 2012: 750908.
25.
Sharquie KE, Al-Dhalimi MA (2003) Keloid in Iraqi
patients. A clinicohistopathologic study. Dermatol Surg 29: 847-851.
26.
Philandrianos C, Kerfant N, Jaloux C Jr, Martinet L,
Bertrand B, et al. (2016) Keloid scars (part I): Clinical presentation,
epidemiology, histology and pathogenesis. Ann Chir Plast Esthet 61: 128-135.
27.
Olaitan PB, Olabanji JK, Oladele AO, Oseni GA (2013)
Symptomatology of keloids in Africans. Sierra Leone J Biomed Res 5: 29-33.
28.
Weledji EP, Ngwane S (2012) The management of
keloids and hypertrophic scars. Darlington County Durham Med J 6: 39-45.
29.
Ogawa R (2017). Keloid and hypertrophic scars are
the result of chronic inflammation in the reticular dermis. Int J Mol Sci 18:
606.
30.
Berman B, Elston DM (2016) Keloid and hypertrophic
scar clinical presentation. Medscape.
31.
Juckett G, Adams HH (2009) Management of keloids and
hypertrophic scars. Am Fam Physician 80: 253-260.
32.
O'Brien L, Jones DJ (2013) Silicone gel sheeting for
preventing and treating hypertrophic and keloid scars. Cochrane Database Syst
Rev 12: 1-76.
33.
Viera MH, Amini S, Valins W, Berman B (2010)
Innovative therapies in the treatment of keloids and hypertrophic scars. J Clin
Aesthet Dermatol 3: 20-26.
34.
Shejbal D, Bedekoviæ V, Ivkiæ M, Kalogjera L, Aleriæ
Z, et al. (2004) Strategies in the treatment of keloid and hypertrophic scars.
Acta clin Croat 43: 417-422.
35.
Smith OJ, McGrouther DA (2014) The natural history
and spontaneous resolution of keloid scars. J Plast Reconstr Aesthet Surg 67:
87-92.
36.
Henriquez CB, Costa F (2003) Resident's thesis
systematization of treatment of keloid. Proceeding at the Plastic Surgery Unit
of the 38th Infirmary of Santa Casa de Misericórdia do Rio de
Janeiro.
QUICK LINKS
- SUBMIT MANUSCRIPT
- RECOMMEND THE JOURNAL
-
SUBSCRIBE FOR ALERTS
RELATED JOURNALS
- Dermatology Clinics and Research (ISSN:2380-5609)
- Journal of Alcoholism Clinical Research
- Journal of Cell Signaling & Damage-Associated Molecular Patterns
- Journal of Spine Diseases
- Journal of Immunology Research and Therapy (ISSN:2472-727X)
- International Journal of Surgery and Invasive Procedures (ISSN:2640-0820)
- International Journal of Anaesthesia and Research (ISSN:2641-399X)