Update on the Management of Keloids

A. Paul Kelly, MD
Keloids are scars, unique to humans, that grow beyond the boundaries of a cutaneous
injury, inammation, burn, or surgical incision. Although benign, keloids are often aesthet-
ically malignant. The etiology of keloids is uncertain. However, we do know that they occur
more often in African-American and Asian than Caucasian patients. There is no one
therapeutic modality that either prevents the formation of keloids or treats active or inactive
lesions. Consequently, there are many therapeutic options. In this review, an approach to
medical and surgical management of keloids is provided, as well as a review of experimen-
tal therapeutic modalities.
Semin Cutan Med Surg 28:71-76 2009 Published by Elsevier Inc.
K
eloids are scars, unique to humans, that grow beyond
the boundaries of a cutaneous injury, inammation,
burn, or surgical incision. However, spontaneous keloids
sometimes develop without a preceding trauma, most com-
monly over the sternum. Although benign, keloids are often
aesthetically malignant, painful, and/or pruritic, but they also
may be asymptomatic. They can occur anywhere on the
body, most often on the earlobes (Fig. 1), shoulders, mid-
chest (Fig. 2), and upper back, but rarely on the hands, feet,
axillae, or scalp. Enlargement can be predicted in areas of the
keloid that have an erythematous border (Fig. 3).
The etiology of keloids is uncertain, especially because
there are no animal models to study. They occur most often
in dark-skinned individuals. African Americans form keloids
more often than Caucasians by a ratio ranging from 5:1 to
16:1. Keloids do not occur in albinos. The author has treated
2 patients with keloids who developed vitiligo. Some of the
vitiliginous lesions were overlying a keloid that resolved in
these areas, but the keloid did not improve in areas covered
by the patients normal-colored skin. The incidence of ke-
loids is approximately equal for male and female patients.
They can occur at any time of life but most commonly in
patients in their 20s and 30s. Although the formation of
keloids clearly involves both genetic and environmental fac-
tors, they are not yet fully understood.
Precipitating Events
Both cutaneous viral and bacterial infections can lead to the
development of keloids, especially in the lesion sites of Afri-
can-American children, unless preventative therapy (eg,
pressure, topical steroids, and imiquimod) is administered
early. Herpes zoster may also cause keloids to form, as well as
pseudofolliculitis barbae (ie, razor bumps), which is most
common among African-American men who shave, and acne
keloidalis nuchae, which is characterized by keloid-like pap-
ules and plaques on the occipital scalp and posterior neck.
Inammatory skin conditions, such as varicella, Bacille
Calmette-Guerin vaccination, folliculitis, and acne (Fig. 4)
may also precipitate the formation of keloids. Other culprits
are thermal and chemical burns, ear-piercing, tattooing, and
fraternity branding.
Diagnosis
Keloids are characterized by excessive deposition of collagen
in the dermis beyond the boundaries of the wound, whereas
hypertrophic scars remain within those boundaries (Fig. 5).
However, it can be difcult to distinguish between early ke-
loids and hypertrophic scars. Unlike hypertrophic scars,
which usually regress in a year or two, keloids typically grow
for several years and then become stable. There are, however,
some keloids that grow for years or even the lifetime of the
patient (Fig. 6). Also, although hypertrophic scars respond
well to therapy, keloids may not.
Preventive Measures
Before providing surgical treatment for keloids, the physician
should know whether the patient, or his/her immediate fam-
ily, has a history of keloid formation. One should note that if
Department of Internal Medicine, Division of Dermatology, Charles Drew
University of Medicine and Science, Los Angeles, CA.
Address reprint requests to A. Paul Kelly, MD, Department of Internal Med-
icine, Division of Dermatology, Charles DrewUniversity of Medicine and
Science, 12021 Wilmington Avenue, Room 4016, Los Angeles, CA
90059-3019. E-mail: apaulkelly@yahoo.com
71 1085-5629/09/$-see front matter 2009 Published by Elsevier Inc.
doi:10.1016/j.sder.2009.04.002
a patient has only earlobe keloids, it does not necessarily
indicate that the individual is prone to keloid formation be-
cause earlobe keloids are common and may occur without
the presence of a positive family history. Other major risk
factors that the patient and the physician must be aware of are
an infected operative site and the type of precipitating injury
(especially thermal or chemical burns). Physicians should
warn at-risk patients not to have their ears pierced, get tat-
toos, or undergo nonessential cosmetic surgery, such as
breast reduction or augmentation, face-lifts, or tummy-tucks.
Treatment
Although no one therapy works best for all keloids, the stan-
dard treatment is intralesional corticosteroids and/or topical
corticosteroids, which inhibit the alpha-2-macroglobulin.
Alpha-2 macroglobulin, when active, normally inhibits col-
lagenase. Thus, the use of intralesional and/or topical corti-
costeroids enables collagenase to be active, enabling collagen
degeneration. In fact, collagenase may prove to be the best
treatment, although a study by Kang et al
1
found that intrale-
sional collagenase was ineffective in treating keloids.
The patient should be warned that the corticosteroid in-
jection sites may become hypopigmented and/or atrophic for
3 to 6 months. An hour before injection, the physician should
apply a thick coating of a topical anesthetic cream such as
EMLA (Rx. AstraZeneca, Wilmington, DE) or LMX4 (Rx.
Ferndale, Ferndale, MI) to the keloid and cover with plastic
wrap. Thereafter, triamcinolone, 10-40 mg mL
1
, should be
Figure 1 The most common site for keloids is the posterior ear lobes.
They are usually larger than anterior ear-lobe keloids.
Figure 2 Keloids on the mid-chest are the least responsive to therapy
and the most common site for spontaneous keloids.
Figure 3 A keloid on the left ank with erythema of the right inferior
border.
Figure 4 Keloids on the back, chest, and shoulder secondary to acne.
72 A.P. Kelly
injected every 2 to 3 weeks with a 27- to 30-gauge needle.
(Note that larger needles will clog more often when inserted
into hard keloids.)
The needle is inserted into the papillary dermis, where
collagenase is produced. Then, the needle should be placed a
little deeper into the dermal-epidermal plane, where the tri-
amcinolone will insert more easily. The physician should
inject the contents of the needle while withdrawing. One easy
way to inject triamcinolone is to use half 10 mg/mL and half
40 mg/mL. This ratio provides adequate strength of triamcin-
olone and ease of injection without clogging the needle as
much as when triamcinolone, 40 mg mL
1
, alone is injected.
If, after 4 injection sessions, the keloid has not begun to
regress or get softer, surgery is recommended.
Other injectable therapies that have been reported to have
varying success are bleomycin, 5 uorouracil (5-FU), and
interferon. Small isolated keloids have been successfully
treated with 5-FU. The response is best when 0.1 mL of
triamcinolone acetonide, 10 mg mL
1
, is added to 0.9 mL of
5-FU, 50 mg mL
1
. This mixture is initially injected into the
keloid 3 times per week and is then adjusted according to the
response. Most keloids require 5 to 10 injections, which are
painful. This type of therapy should be limited to small ke-
loids. Interlesional bleomycin has been successful in atten-
ing keloids via a multipuncture technique at a concentration
of 1.5 IU/mL with the use of a needle and syringe or Dermajet
(Robbins Instruments Inc, Chatham, NJ).
2,3
Complete at-
tening occurred in 6 of 13 cases.
Surgical Excision
When performing surgery, the physician should avoid mak-
ing mid-chest incisions and crossing joint spaces, should
follow skin creases where possible, and should close the
wound with minimal tension. Patients who have used sys-
temic steroids or isotretinoin during the previous 6 months
can have poor treatment results with surgery because both of
these medications can impair wound healing. All patients
who undergo excisional surgery must have explicit preoper-
ative and postoperative instructions because postoperative
compliance is an extremely important part of successful sur-
gical therapy. Prolonged pressure is often effective in pre-
venting recurrence of keloids after surgical excision. An elas-
tic garment covering the postoperative site should be worn
16 to 20 hours a day, beginning immediately after complete
wound healing. Pressure seems to decrease -macroglobu-
lins, which normally would inhibit collagenase breakdown of
collagen. Pressure also reduces mast cells, which are in-
creased in keloids and may be the cause of keloid pruritus.
To anesthetize the site, the physician should use a mixture
of equal parts triamcinolone acetonide, 40 mg mL
1
, and 2%
lidocaine with epinephrine (1:1000). For patients with a his-
tory of keloid formation, as noted previously, one should
avoid making mid-chest incisions and crossing joint spaces
and should follow crease lines, if possible. If the keloid has a
narrow base, it is usually sufcient to make a simple elliptic
excision and undermine the base, then close with sutures.
For keloids with large bases or large nonpedunculated ear-
lobe keloids, the procedure is more complex. A tongue-line
incision approximately one-fth the size of the keloid from
its border to the attest-looking surface should be made, the
keloid excised, and then the site closed with the tongue-like
ap of keloid tissue (Fig. 7). In cases in which the skin is not
smooth, the physician can insert a tissue expander and wait
several months before excising the keloid and closing the
Figure 5 Hypertrophic scar of the forearm.
Figure 6 Keloid on the chest that has been slowly growing for 15
years.
Figure 7 The postexcision site is closed with a tongue-like ap.
Update on the management of keloids 73
wound primarily with the least amount of tension possible.
One should wait 10 to 20 days to remove sutures, especially
after earlobe keloid excision.
Adjunct Therapy
Unfortunately, excision alone has a recurrence rate of 50%,
so adjunct therapy is advised (Fig. 8). The most common
adjunct is the injection of triamcinolone acetonide, 40 mg
mL
1
, into the postoperative site every 2 to 3 weeks 4,
beginning 1 week after suture removal. The maximum dos-
age advised per injection session is 5 mL. To anesthetize the
site, use a mixture of equal parts triamcinolone acetonide, 40
mg mL
1
, and 2% lidocaine with epinephrine. If injection is
still too painful, inject 1% lidocaine into the perilesional area
of the keloid. The steroid slows wound healing; therefore,
sutures should remain in place for 10 to 20 days. Later, if the
postoperative site begins enlarging, intralesional triamcino-
lone should be readministered. Daily use of urandrenolide
(Cordran) tape (Rx. Watson Laboratories, Corona, CA) or a
potent topical steroid is recommended as an adjunct to the
injections.
Other adjunct therapies include the following:
Pressure garments combined with a class 1 topical ste-
roid, beginning 1 week after suture removal, helps pre-
vent recurrence.
Flurandrenolide tape can be applied daily and left on 12
to 20 hours.
Daily use of silicone gel sheeting can also be effective.
Another topical agent that may be successful for treating
keloids is Curad scar therapy (Beirsdorf, El Paso, TX). It
is a polyurethane, silicone-free adhesive that can be used
on new or old keloids and may be applied to any part of
the body, including the face. It is left on for 12 hours
a day for as long as the keloid is becoming atter and
then applied weekly to prevent recurrence.
For posterior pedunculated earlobe keloids, shaving fol-
lowed by pressure hemostasis and postoperative daily
use of a pressure earring with silicone backing may pre-
vent recurrence.
A million units of interferon alpha-2 per linear centi-
meter injected into the excision site immediately after
surgery and 1 to 2 weeks later is also effective, according
to Berman and Flores,
4
who reported an 18.7% recur-
rence rate, whereas their recurrence rate with excision
alone was 51%. (If the site is long, requiring more than
5 million Uof interferon alpha-2, the physician should
premedicate the patient with acetaminophen to help
prevent the ulike symptoms that can be caused by the
interferon.) The major limiting factor in the use of alpha-
interferon is its high cost.
Imiquimod cream, applied immediately after surgery
and daily for 8 weeks, is another adjunct therapy. Its use
is not advised until 4 to 6 weeks after surgery for patients
with incisions that are large, under tension, or closed
with aps or graphs, which may splay or dehisce. Ac-
cording to Berman and Kaufman,
5
one half of the pa-
tients also developed hyperpigmentation. Some subjects
also experienced marked irritation for 3 to 7 days before
being able to resume treatment.
Topical tacrolimus has been touted as preventing the
recurrence of keloids, whereas pentoxifylline (Trental)
400 mg t.i.d. has shown limited success.
6,7
Two older therapies that deserve mention are metho-
trexate and colchicine, both of which have shown some
success. Methotrexate, 15-20 mg, in a single dose every
4 days, starting a week after surgery and continuing for
3 to 4 months, induces folic acid deciency, resulting in
poor collagen formation. Colchicine may work by inhi-
bition of collagen synthesis and collagenase stimulation.
(However, Kang et al
1
found that collagenase, when in-
jected intralesionally, was ineffective in the treatment of
keloids.)
Super potent (class 1) topical corticosteroids, such as
clobetasol propionate, are useful when applied daily or
b.i.d.
Antihistamines can be used for pruritus, although pos-
sible drowsiness may be a problem for some patients.
Sting stop is an herbal remedy that sometimes stops the
pruritus when applied 3 to 4 times a day (Google Sting
Stop for more information).
Other Medical Therapies
Verapamil, a calcium-channel blocker or calcium-ion antag-
onist, blocks the synthesis of collagen, glycosaminoglycans,
and bronectins. In one study, patients were treated with
intralesional verapamil, 2.5 mg/mL, after excision during a
2-month period.
8
Twenty-two keloids (55%) in 16 patients
(52%) were cured by this treatment modality. Relaxin is a
growth factor that can stimulate collagenase activity. It has
been used in several trials for the treatment of scleroderma.
9
D-penicillamine, another drug that has been used in the
treatment of scleroderma,
10
is an immunosuppressive agent
that interferes with the cross-linking ability of collagen. It
may be useful in the treatment of keloids. Clinical trials with
Figure 8 A recurring keloid; each time after surgery, it grew larger.
However, the patient did not use adjunctive therapy as prescribed.
On her initial visit, the keloid measured a 3 by 20.3 cm; it subse-
quently tripled in size after 3 surgeries.
74 A.P. Kelly
topical zinc, tretinoin, and cyclosporin have provided mixed
results in their therapeutic effectiveness.
11-14
Alternatives to
excision are cryosurgery, laser surgery, and radiation. They
can also be useful adjuncts to excision.
Cryosurgery
Cryosurgery can be used as a monotherapy or to produce
mild edema of the keloid for easier injection of intralesional
steroids. When used before injections, the freeze time is 10 to
15 seconds. As a monotherapy, use 2 courses of 15-20 sec-
ond freeze-thaw cycles every 3 weeks. The patient should be
warned of the possibility of hyperpigmentation for 6 to 12
weeks, which may occur with a freeze time of 20 seconds.
However, a longer freeze time may cause hypopigmentation
lasting longer than a year. To decrease morbidity, the patient
should take 2 adult aspirin 1 hour before treatment and apply
clobetasol propionate, 0.05% ointment t.i.d. 2 days, after
cryosurgery.
Laser Therapy
The jury is still out on the success of lasers in keloid therapy.
Although numerous studies have been published on the sub-
ject, so far no laser has proved to be a panacea. The carbon
dioxide laser can be used to debulk large lesions but when
used as monotherapy, there is often a recurrence rate of
70%. The Nd:YAG 1064-nm laser was successful in im-
proving keloids in 16 of 17 patients, according to Sherman
and Rosenfeld,
15
but their study provides little follow-up
information. The 585-nm ash lamp pumped pulsed-dye
laser has shown some success in treating sternotomy scars,
16
especially when used in conjunction with intralesional triam-
cinolone injected every 3 weeks.
17
Radiation
Radiation as a monotherapy has not shown much success
except in large doses. However, large doses can increase the
risk of squamous-cell carcinoma at the treated site 15 or more
years later. Radiation is more successful as an adjunct to
surgery, used during the rst 2 weeks after excision when the
broblasts are proliferating. The usual dosage is either 300
rads (3 Gy) q.o.d. for 5 courses or 500 rads (5 Gy) q.o.d. for
3 courses starting immediately after surgery. Use of intersti-
tial radiotherapy with iridium 192 postoperatively reduced
the recurrence of keloids by 20 to 30%. Single-fraction radio-
therapy after extralesional excision was reported by Ragoow-
ansi et al
18
to be effective in preventing recurrence of high-
risk keloids that did not respond to prior treatment.
Although keloid therapy consists of many different combina-
tions and permutations (Table 1), there is no universally
efcacious monotherapy that will either cure keloids or pre-
vent their formation.
Possible Future
Therapeutic Agents
Several possible treatments still in the experimental stage
include hydroquinone, G6PD, and hyperbaric oxygen.
Hydroquinone or Other Bleaching Agents
Bleaching appears to be a promising therapy. The rationale is
that albino patients do not develop keloids and vitiligo often
causes the underlying keloid to regress. Hydroquinone
works best if used within the rst 5 months of keloid forma-
tion. If an excision is performed rst, treat the excision site
plus a 1- to 2-cm margin, being sure to include all suture
sites.
Glucose-6-Phosphate
Dehydrogenase Deciency (G6PD)
African-American patients have a greater incidence of G6PD
than Caucasian patients and, in the authors experience, pa-
tients with keloids have a greater incidence than those who
dont. Thus, an agent to lower or block G6PD might be suc-
cessful in treating keloids.
Hyperbaric Oxygen
Because low oxygen tension (hypoxia) stimulates broblasts,
high oxygen tension may do the opposite. Studies are being
conducted to compare how broblasts respond to low and
high oxygen tension.
Future Research
There is a need for further research to determine the etiology
of keloids. Unfortunately, there is no animal model for re-
search. Hoof animals do develop keloid-like lesions on their
extremities, as do eagles and the vulture family of birds. How-
Table 1 Keloids: Therapeutic Options
Topical
Corticosteroids
Imiquimod
Tacrolimus
Flurandrenolide tape
Silicone gel sheeting
Curad scar therapy
Intralesional
Corticosteroids
5-FU
Bleomycin
Interferon alpha-2b
Surgical
Excision with primary closure
Excision with second-intention closure
Excision with aps or grafts
Laser surgery
Cryosurgery
Physical
Pressure garments
Pressure earrings
Suture amputation
Oral medications
Methotrexate
d-Penicillamine
relaxin
colchicine
Update on the management of keloids 75
ever, in these animals, the lesions clear without therapy when
the offending agent is withdrawn.
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