|Year : 2015 | Volume
| Issue : 1 | Page : 23-28
Recurrent earlobe keloids: a combined intralesional injection of 5-fluorouracil and excision
Essam A Taman1, Ahmed Aamer MD 2
1 Department of Plastic Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Dermatology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||10-Mar-2015|
|Date of Acceptance||07-Jun-2015|
|Date of Web Publication||7-Aug-2015|
Dermatology and Venorology, Faculty of Medicine, Al Azhar University, New Damietta, Cairo
Source of Support: None, Conflict of Interest: None
Management of keloids is still controversial. Many treatment options have been proposed for earlobe keloids, including both surgical and nonsurgical methods. However, no single method has been found completely satisfactory.
To find a new treatment technic that decrease recurrent rate earlobe keloids,
The present study aimed to evaluate the eff ect of a combination of intralesional injection of 5-fl uorouracil (5-FU) and surgical excision on the recurrence rate of earlobe keloids.
From January 2012 to March 2014, a prospective study was conducted on 50 earlobe keloids on 40 patients with recurrent earlobe keloid, which was bilateral in 10 cases and unilateral in 30 cases. The patients were treated with a combination of intralesional injection of 5-fluorouracil and excision. The ages of the patients ranged from 16 to 40 years (mean age was 26.27 ± 5.16 years). The cause of keloids was ear piercing in all cases. The largest lesion was 4 cm in its greatest dimension and the smallest was 1.5 cm.
Improvement occurred in 64% of patients with acceptable esthetic results and recurrence occurred in 36% of patients. No relevant individual changes in serum values or blood chemistry were seen.
This technique is safe, well tolerated, and effective in decreasing or almost preventing the recurrence of earlobe keloids. We recommend this technique for recurrent earlobe keloids with poor response to intralesional therapy.
Keywords: 5-fluorouracil, earlobe keloid, excision
|How to cite this article:|
Taman EA, Aamer A. Recurrent earlobe keloids: a combined intralesional injection of 5-fluorouracil and excision. Egypt J Dermatol Venerol 2015;35:23-8
|How to cite this URL:|
Taman EA, Aamer A. Recurrent earlobe keloids: a combined intralesional injection of 5-fluorouracil and excision. Egypt J Dermatol Venerol [serial online] 2015 [cited 2020 May 31];35:23-8. Available from: http://www.ejdv.eg.net/text.asp?2015/35/1/23/162464
| Introduction|| |
The name keloid is derived from the Greek word 'chele', which means crab claw, referring to the way in which these lesions extend into normal tissue .
The increasing trend for cosmetic multiple ear piercing suggests that earlobe keloids will become a more frequent part (2.5%) of dermatological and plastic surgery practice .
Earlobe keloids occur after cosmetic ear piercing, trauma, infection, or burns, or spontaneously. These keloids are highly resistant to treatment and can be followed by severe cosmetic implications .
Pain and itching are common presentations in keloids and are associated with abnormalities in small nerve fiber function, suggesting a small nerve fiber neuropathy .
The treatment of keloid scarring remains one of the most difficult challenges in plastic surgery. The availability of a large number of treatment modalities suggests that none of these techniques provide a good consistently and satisfying result .
Surgical excision alone of keloids results in a high rate of recurrence (45-100%). Combining surgery with other modalities reduces the recurrence rate of keloids to less than 50% .
Flurouracil (5-FU) inhibits fibroblast proliferation and decreases collagen production. As a result of its initial inhibition of nuclear replication 5-FU application may be a result of its initial inhibition of nuclear replication. This may have a permanent effect by its presence, even in small quantities; and by a failure of the tissue to eliminate it. The effect on inflammatory markers is more complex and unclear .
| Aim of the study|| |
The present study aimed to evaluate the effect of a combination of intralesional injection of 5-fluorouracil (5-FU) and surgical excision on the recurrence rate of earlobe keloids.
| Patients and methods|| |
This is a prospective study including 50 earlobe keloids from 40 patients with recurrent earlobe keloids, which was bilateral in 10 cases and unilateral in 30 cases. They were recruited between January 2012 and March 2014 from both Dermatology and Plastic Surgery departments (Al-Azhar University Hospital). We included only cases with recurrent earlobe keloids.
Exclusion criteria included the following: pregnancy, lactation, significant cardiac disease, active infections, allergic reactions, recovering from surgery conducted the previous month, systemic steroid therapy within 4 months from study entry, cytotoxic therapy, presence of renal or hepatic diseases, thyroid dysfunction, or diabetes mellitus, infants, being elderly, and isotretinoin therapy.
The ages of the patients ranged from 16 to 40 years; the cause of keloids was ear piercing in all cases. The study protocol was approved by the local ethical committee of Al-Azhar University Hospital and informed consent was obtained from all participants after they were given an explanation of the study protocol. Thereafter, complete history taking and general examination were carried out. The largest lesion was 4 cm and the smallest was 1.5 cm.
All cases were treated with combined intralesional injection of 5-FU and marginal excision. The patients were followed up for 6 months to assess recurrence.
Protocol for intralesional injection: the total dose of 5-FU injected per session ranged from 50 to 150 mg at a concentration of 50 mg/ml (enough to cause slight blanching) once weekly for 4 weeks . The injection was carried out after sterilization and local anesthetic spray.
Surgical excision was performed at the end of the fifth week after injection under local anesthesia; all earlobe keloids were marked and excised. Hemostasis was achieved with electrocautery. Wound closure was performed with 5-0 polypropylene sutures and the wound was dressed with sterile wound tapes.
Clinical evaluation: this included subjective criteria such as pain and itching, and objective criteria such as color and size, measured at maximal length, width, and height (expressed in square centimeters). The keloid scar was assessed according to the keloid scar score, before therapy and at the end of therapy, based on the Vancouver score, which was modified to take into account symptoms such as itching and pain, described as characteristic of keloid scars. Best scar score = 0; worst scar score = 8 .
Photographs were taken before therapy, at the end of therapy, and 6 months after excision.
Laboratory investigations included complete blood picture, liver function tests (SGPT and SGOT), and serum creatinine before therapy and at the end of therapy.
The occurrence of any complications during therapy was recorded [Table 1].
| Results|| |
In the present work, ages ranged from 16 to 40 years with a mean of 26.27 ± 5.16 years; there was no significant difference between scar length and width after intralesional injection when compared with their values before injection. In contrast, there was significant decrease in both scar height and keloid score after injection when compared with values before injection [Table 2]. In addition, there was no significant difference as regards hemoglobin, AST, and ALT after surgery when compared with their values before surgery [Table 3]. Improvement of symptoms (pain and itching) and colors was observed after injection [Table 2]. Assessment of keloids score before and after intralesional injection of 5-FU showed improvement in 50% of patients after intralesional injection of 5-FU. The results of surgical excision after intralesional 5-FU showed 64% improvement with acceptable esthetic results; recurrence was seen in 36% of patients. The complications observed with 5-FU were purpura at the injection site (40%), pain in 100%, and localized superficial tissue sloughing in 12%. In addition, hyperpigmentation was observed at the site of injection in 22 earlobes (44%). No cases of wound complication after excision were seen [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7] and [Figure 8].
|Table 2: Age and scar characteristics before and after intralesional 5-fluorouracil injection|
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| Discussion|| |
Keloids are benign fibrous growths that develop as a result of proliferation of dermal tissue following trauma or injury to the skin . The basis of keloid formation has not been fully understood. Some authors reported that keloid-derived fibroblasts produce increased amounts of collagen per cell in tissue culture; however, there have also been controversial reports .
Ploplis et al.  reported that the fibroblasts appear to function autonomously and demonstrate continued collagen synthesis in vitro in the absence of any humoral substances. These fibroblasts and the collagen produced by them have been the target of antikeloid therapies .
In addition, in keloid macrophage release, interleukin-1, important for extracellular matrix degradation, may also be reduced, as reported by Amadeu et al. . The exact pathophysiological mechanism for keloid formation, however, remains largely unknown, although tension has been suggested to be one factor, with another being skin pigmentation .
The preferred initial treatment for keloids is intralesional injection of triamcinolone at most of the centers; however, this may induce hypopigmentation and may lead to atrophy, telangiectasia, necrosis, and ulceration ,.
5-FU, a pyrimidine analog with antimetabolite activity, had been studied as an adjunct to glaucoma filtering surgery to inhibit wound healing. Also, 5-FU has been shown to produce a reversible delay of fibroblast growth in subconjunctival and scleral tissues, as shown by Chang et al. .
This fundamental work also highlighted important points about the effects of 5-FU on fibroblasts. In addition, most research written on this subject recommends that this work be followed up by more trials and investigations ,.
In the present study, we used a dose of 5-FU that ranged from 50 to 150 mg at a concentration of 50 mg/ml once weekly for 4 weeks. Also, Gupta and Kumar  used the same dose and schedule for intralesional injection of keloid scars. Uppal et al.  used a single dose of 5-FU (25 mg/ml) on keloid scars as a single touch for 5 min after extralesional excision with good clinical and histological outcome. Also, they concluded that 5-FU in some way altered the functional activity of fibroblasts without being toxic to them.
The side effects observed in the earlier study with 5-FU were purpura at the injection site (40%), pain in 100%, and localized superficial tissue sloughing in 12%. We, however, observed hyperpigmentation at the site of injection in 22 earlobes (44%). Gupta and Kumar  reported hyperpigmentation in their cases and attributed it to the difference in skin color.
Fortunately, in the present study no relevant individual changes in serum values or blood chemistry were observed.
Injection of 5-FU led to no significant differences as regards the length and width of keloid scars, whereas the height of the keloid scars showed a significant change. Improvement in symptoms was observed after injection of 5-FU. This finding is comparable to that reported by Uppal et al. , who reported that the keloid scar score revealed a perceived improvement in those treated with 5-FU, compared with the control specimens, during the 6-month follow-up period.
In the present study, overall, more than half of the patients treated with 5-FU showed significant (50%) improvement in keloids as regards height, symptoms, and keloid score index. These results are well comparable to the results of other singly used treatment modalities. In the present study the recurrence rate of excised keloids after intralesional injection of 5-FU was 36% with a follow-up of 6 months. Mustoe et al.  found that surgical excision alone of keloids results in a high rate of recurrence (45-100%). Combining surgery with steroid injection reduces the recurrence rate of keloids to less than 50%, with the combination of surgery and preoperative radiation therapy reducing recurrence to 10%.
Further, Nd:YAG and CO 2 laser, when used alone, produce a good initial response in almost all patients; however, the keloids recur rapidly in almost two-thirds of patients ,.
As suggested by Fitzpatrick  and Alster and Handrick  intralesional 5-FU can be combined with other treatment modalities like intralesional corticosteroids, laser, and cryosurgery to achieve a better outcome. This may also reduce the duration of treatment and side effects related to prolonged therapy with a single agent. Fitzpatrick  reported the use of intralesional 5-FU mostly in combination with other modalities for the treatment of hypertrophic scars and keloids.
Intralesional 5-FU can be used successively as monotherapy as well as in combination with intralesional corticosteroids to treat hypertrophic scars and keloids. The rationale for its use is sound, and there is a lack of side effects. It may warrant further investigation and wider use as an alternative to steroid injections in difficult-to-treat patients .
Fitzpatrick and Manuskiatti  concluded that clinical improvement of keloid scars after treatment with intralesional corticosteroid, alone or in combination with 5-FU, with 5-FU alone, and with pulsed dye laser seemed comparable, with the exception of the incidence of adverse reactions, which were most common with intralesional corticosteroid. Intralesional 5-FU is comparable to other therapies.
Cohen and Peacock  suggested that keloid fibroblasts might represent a subgroup of increased collagen-producing fibroblasts that have either 'gone away' or have been preferentially selected during the process of acute inflammation, which in turn affects underlying dermal fibroblast growth and collagen secretion to produce the keloid.
Bertolami et al.  demonstrated that a local state of hypoxia exists in keloids, which can be attributed to two plausible mechanisms implicated in the development of fibrotic wounds, ongoing fibroplasia or inflammation, due to an excessive accumulation of extracellular matrix and increased levels of vascular endothelial growth factor in keloid scars, suggesting pathological processes, leading to prolonged inflammation and an altered balance in extracellular matrix metabolism.
Amadeu et al.  reported that abnormal vascularization can be involved in the development of hypertrophic scars and keloids. Compared with normal skin and normal scars, hypertrophic scars and keloids have a distinct pattern of vascularization. Bertolami et al.  reported that deficient or overabundant levels of vascular endothelial growth factor contribute to the pathophysiology of impaired wound healing, based on the mechanisms of keloid formation.
In short, our results indicate that this technique is safe, well tolerated, and effective in decreasing or almost preventing the recurrence of earlobe keloids. However, we recommend this technique for recurrent earlobe keloids with poor response to intralesional therapy. There remains a significant need for further randomized, controlled trials of all available keloid therapies and systematic, quantitative reviews of the literature to ensure optimal management of keloid scars.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Greenhalgh DG. Consequences of excessive scar formation: dealing with the problem and aiming for the future. Wound Repair Regen 2007; 15
Ogawa R, Miyashita T, Hyakusoku H, Akaishi S, Kuribayashi S, Tateno A Postoperative radiation protocol for keloids and hypertrophic scars: statistical analysis of 370 sites followed for over 18 months. Ann Plast Surg 2007; 59
Stahl S, Barnea Y, Weiss J, Amir A, Zaretski A, Leshem D, et al
. Treatment of earlobe keloids by extralesional excision combined with preoperative and postoperative "sandwich" radiotherapy. Plast Reconstr Surg 2010; 125
Verhaegen PD, van Zuijlen PP, Pennings NM, van Marle J, Niessen FB, van der Horst CM, Middelkoop E. Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin: An objective histopathological analysis. Wound Repair Regen 2009; 17
Rasheed IA, Malachy AE. The management of helical rim keloids with excision, split thickness skin graft and intralesional triamcinolone acetonide. J Cutan Aesthet Surg 2014; 7
Gold MH, Berman B, Clementoni MT, Gauglitz GG, Nahai F, Murcia C. Updated international clinical recommendations on scar management: part 1 - evaluating the evidence. Dermatol Surg 2014; 40
Haurani MJ, Foreman K, Yang JJ, Siddiqui A. 5-Fluorouracil treatment of problematic scars. Plast Reconstr Surg 2009; 123
:139-148. discussion 149-151.
Gupta S, Kumar B. Intralesional cryosurgery using lumbar puncture and/or hypodermic needles for large, bulky, recalcitrant keloids. Int J Dermatol 2001; 40
Uppal R, Khan U, Kakar S. The effect of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after exteralesional excision. Plast Reconstr Surg 2001; 108
Zouboulis C, Orfanos C. Cryosurgical treatment. In: Harahap M, editor. Surgical techniques for cutaneous scar revision. New York: Dekker; 2000. 234.
English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatol Surg 1999; 25
Ploplis VA, Wilberding J, McLennan L, Liang Z, Cornelissen I, DeFord ME, et al
. A total fibrinogen deficiency is compatible with the development of pulmonary fibrosis in mice. Am J Pathol 2000; 157
Low SQ, Moy RL. Scar wars strategies. Target collagen. J Dermatol Surg Oncol 1992; 18
Amadeu T, Braune A, Mandarim-de-Lacerda C, Porto LC, Desmoulière A, Costa A. Vascularization pattern in hypertrophic scars and keloids: a stereological analysis: Pathol Res Pract 2003; 199
Ishihara H, Yoshimoto H, Fujioka M, Murakami R, Hirano A, Fujii T, et al
. Keloid fibroblasts resist ceramide-induced apoptosis by overexpression of insulin-like growth factor I receptor. J Invest Dermatol 2000; 115
Urioste SS, Arndt KA, Dover JS. Keloids and hypertrophic scars: review and treatment strategies. Semin Cutan Med Surg 1999; 18
Chang MR, Chang Q, Lee D. Basic science and clinical aspect of wound healing in glaucoma filtering surgery. J Ocul Pharmacol Ther 1998; 14
Lebwohl M. From the literature: intralesional 5-FU in the treatment of hypertrophic scars and keloids: clinical experience. J Am Acad Dermatol 2000; 42
Pittet B, Rubbia-Brandt L, Desmoulière A, Sappino AP, Roggero P, Guerret S, et al
. Effect of gamma-interferon on the clinical and biologic evolution of hypertrophic scars and Dupuytren′s disease: an open pilot study. Plast Reconstr Surg 1994; 93
Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, et al
. International Advisory Panel on Scar Management. International clinical recommendations on scar management. Plast Reconstr Surg 2002; 110
Alster TS, Handrick C. Laser treatment of hypertrophic scars, keloids, and striae. Semin Cutan Med Surg 2000; 19
Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg 1999; 25
Fitzpatrick R, Manuskiatti W. Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flash lamp-pumped pulsed-dye laser treatments: Arch Dermatol 2002; 138
Cohen I, Peacock E. Keloids and hypertrophic scars. In: editors McCarthy JG. Plastic Surgery. Philadelphia, PA: Saunders 1990. 732-747.
Le AD, Zhang Q, Wu Y, Messadi DV, Akhondzadeh A, Nguyen AL, et al
. Elevated vascular endothelial growth factor in keloids: relevance to tissue fibrosis. Cells Tissues Organs 2004; 176
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2], [Table 3]