ORIGINAL ARTICLE

Epidemiology and Risk Factors for Pathologic

Scarring After Burn Wounds
Ezio Nicola Gangemi, MD; Dario Gregori, MA, PhD; Paola Berchialla, PhD; Enrico Zingarelli, MD;
Monica Cairo, MD; Daniele Bollero, MD; Jamal Ganem, MD; Roberto Capocelli, MD; Franca Cuccuru, MD;
Pompeo Cassano, MD; Daniela Risso, MD; Maurizio Stella, MD

Objective: To describe the clinical characteristics of post-
burn scars and determine the independent risk factors
specific to these patients. While burns may generate wide-
spread and disfiguring scars and have a dramatic influ-
ence on patient quality of life, the prevalence of post-
burn pathologic scarring is not well documented, and the
impact of certain risk factors is poorly understood.
Methods: A retrospective analysis was conducted of the
clinical records of 703 patients (2440 anatomic burn sites)
treated at the Turin Burn Outpatient Clinic between Janu-
ary 1994 and May 15, 2006. Prevalence and evolution
time of postburn pathologic scarring were analyzed with
univariate and multivariate risk factor analysis by sex,
age, burn surface and full-thickness area, cause of the burn,
wound healing time, type of burn treatment, number of
surgical procedures, type of surgery, type of skin graft,
and excision and graft timing.
tients (77%): 310 had hypertrophic scars (44%); 34, con-
tractures (5%); and 196, hypertrophic-contracted scars
(28%). The hypertrophic induction was assessed at a me-
dian of 23 days after reepithelialization and lasted 15
months (median). A nomogram, based on the multivar-
iate regression model, showed that female sex, young age,
burn sites on the neck and/or upper limbs, multiple sur-
gical procedures, and meshed skin grafts were indepen-
dent risk factors for postburn pathologic scarring (Dxy
0.30).
Conclusion: The identification of the principal risk
factors for postburn pathologic scarring not only
would be a valuable aid in early risk stratification but
also might help in assessing outcomes adjusted for
patient risk.

Results: Pathologic scarring was diagnosed in 540 pa- Arch Facial Plast Surg. 2008;10(2):93-102

Author Affiliations:
Department of Plastic and
Reconstructive Surgery, Burn
Center, Traumatological Center
(Drs Gangemi, Zingarelli, Cairo,
Bollero, Ganem, Capocelli,
Cuccuru, Cassano, Risso, and
Stella), and Department of
Public Health and Microbiology,
University of Turin (Drs Gregori
and Berchialla), Turin, Italy.
A
LTHOUGH THE MODERN
concepts of burn care date
from World War II, major
advances in the treatment of
massive burn injuries have
been made only since the 1960s.1 Indeed,
improved critical care with optimized fluid
and electrolyte management combined with
new surgical techniques and the use of skin
allografts and cultured skin cells have had
a strong impact on the natural history of
such injuries.2-4 Thus, the survival rate of
patients with major burns has greatly in-
creased over the last few decades. Unfortu-
nately, humans do not heal through a pro-
cess of tissue regeneration. Scarring is
therefore the rule and remains a lasting re-
minder of the insult to the patient and the
outside world alike. Moreover, minimal
scarring, in terms of the quality of the re-
parative processes and absence of patho-
logic alterations of the wound healing, is one
of the main requirements for recovery.
Therefore, care of the burn patient must be
oriented toward the best possible func-
tional and cosmetic rehabilitation.
Burn scars have a dramatic influence on
a patient’s quality of life. They have been as-
sociated with anxiety, social avoidance, de-
pression, a disruption in activities of daily
living, the onset of sleep disturbances, and
all of the consequent difficulties in return-
ing to normal life after physical rehabilita-
tion.5 Normotrophic scars, which repre-
sent the best clinical end point for treatment,
are characterized by minor alterations in
skin properties. Perturbations of cutane-
ous wound-healing mechanisms give rise to
the formation of pathologic scars.
There is still much controversy as to the
pathophysiology, taxonomy, and clinical
course of postburn scarring. Indeed, few epi-
demiologic observations and data have been
published on this question. Furthermore,
most of the clinical studies are not homo-
geneous and often do not include an ad-
justed population. Thus, the estimates of
prevalence determined by these studies vary
widely and can be used only as suggestive
and advisory data in daily practice. Like-
wise, knowledge of the risk factors for patho-
logic scarring is poor, based on supposi-

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Table 1. Clinical Classification of Pathologic Postburn Scars
Scar Type a Scar Diffusion Scar Evolution b
Normotrophy NA NA
Hypertrophy Generalized, localized Short-term, intermediate,
long-term
Hypertrophy and Generalized, localized Short-term, intermediate,
contracture long-term
Contracture NA NA
Atrophy NA NA
Abbreviation: NA, not applicable.
a Type classification as described by Magliacani et al.18
b Scar evolution was evaluated according to the groups described by Muir.19
tions derived from case studies, opinions, and personal
expert experiences with no strong statistical correlation.
Moreover, in the literature reports, scars have a poorly de-
fined anatomopathologic classification; laboratory mark-
ers of induction or remission of abnormality are not re-
ported; and there is a lack of sensitive and specific methods
to aid in making an objective evaluation.
Generally, pathologic scarring seems to have a higher
prevalence after burns than after surgical procedures or other
traumatic lesions. Only a few studies have developed an
analysis of prevalence and description of postburn patho-
logic scarring. Deitch et al6 analyzed 100 patients with non-
surgical burn wounds considering some presumed risk fac-
tors. The results showed a 38% prevalence of pathologic
scars (hypertrophy and keloid). When the prevalence was
calculated for a single anatomic burn area, it dropped to
26%. Stella7 and Bombaro et al8 describe both type and evo-
lution of the scarring phenomenon in patients with differ-
ent burn surface areas (BSAs) and report a 70% preva-
lence of pathologic scars (hypertrophy, hypertrophy with
contracture, contracture, and atrophy). Dedovic et al9 evalu-
ated the cases of more than 700 children 15 years or younger
and reported a prevalence of at least 32%. Finally, Spurr
and Shakespeare10 investigated the occurrence of scars in
children younger than 5 years with the same pattern and
nature of burn injury and reported at least 50% patho-
logic scarring.
The factors involved in pathologic scar formation are
still under debate, and their complexity, especially with
burns, is well known. Paradoxically, nothing is known
of what variables are implicated in the normotrophic
scarring process, which interests many patients.7 Deitch
et al6 report a substantial difference between prevalences
calculated by single patients vs those calculated by single
areas. These data imply that pathologic scarring may
involve a local process that depends on the injured site,
with the thorax, upper limbs, and feet being at increased
risk. Unfortunately, this association has not been con-
firmed.
The pathologic scar seems to have the same prevalence
in both sexes. Borsini et al11 show that hypertrophy is more
common in young patients and that evolution seems to be
longest in children. On the contrary, scarring often evolves
more rapidly in elderly patients.11 Hypertrophy is directly
correlated with burn extension and occurs more fre-
quently when the burn is caused by flame.
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The literature has documented race as a risk factor for
pathologic scarring, particularly keloids, with black pa-
tients bearing a 2-fold risk compared with Hispanic and
Asian patients.6,12 These data suggest that genetics play an
important role in the pathogenesis of scarring; indeed, some
articles seem to support this hypothesis.13-15 It seems that
such local factors as burn depth, the presence of infection
in the wound bed, and healing delay have a relevance.6
Few studies consider the type of surgical treatment:
generally, treatment with a full-thickness skin graft leads
to a lower prevalence of contracture than treatment with
a partial-thickness skin graft or spontaneous healing.16
On the contrary, Yannas17 suggests that treatment of the
excised burn with biological or biosynthetic cutaneous
substitutes improves scar quality, possibly because these
treatment techniques allow for regeneration rather than
repair of the normal skin layers.
Herein, we describe the clinical characteristics and evo-
lution of postburn scarring in a wide population, deter-
mine the factors associated with an increased risk of patho-
logic scarring, and establish useful guidelines for deter-
mining a reliable prognosis and the best treatment options.
METHODS
Beginning in January 1994, The Department of Plastic and Re-
constructive Surgery–Burn Center of The Turin Traumato-
logic Hospital has made use of a standard form for the collec-
tion of data regarding the scarring process. Clinical histories
are compiled by consulting the patient’s clinical notes during
their initial hospitalization as well as the details recorded dur-
ing outpatient clinic visits and/or subsequent hospitalizations
for corrective surgery.
The present cohort was made up of 703 patients and in-
cluded a total of 2440 anatomic burn sites. All patients were
enrolled into a surveillance program after the completion of the
burn wound healing phase to control and/or treat the post-
burn scarring as necessary. During this study, the type of scar
was defined on the basis of the morphologic classification de-
scribed by Magliacani et al,18 and the scar evolution was evalu-
ated according to the classification groups described by Muir19
(ie, in days from manifestation until complete remission)
(Table 1).
Patients were given a weekly clinical examination until the
second month after complete reepithelialization, and from the
third month, on average, they were visited monthly until the
sixth month (more frequently if deemed necessary). Through-
out this period a number of characteristics were evaluated
(Table 2): sex, age, total burn surface and full-thickness area,
cause of the burn, and wound healing time. If the burn involved
more than 1 anatomic area, each burn site (Figure 1) was evalu-
ated individually for type of burn treatment (medical or surgi-
cal), number of surgical procedures, type of surgical approach (ex-
cision and coverage with autologous skin grafts, Alexander
technique, dermal abrasion, or another technique), type of skin
graft (sheet or meshed), and excision and graft timing.
The diagnosis of pathologic or normotrophic scarring was
based on the clinical evaluation. Our primary objective was to
describe the severity and characteristics of pathologic scarring
as it presents in the clinical environment.
The scars were classified as normotrophic (1) when they as-
sumed characteristics similar to those of the surrounding healthy
skin in terms of thickness, color, and pliability; (2) when they
were only slightly hypopigmented or hyperpigmented; or (3)
when any erythema, with or without itching, disappeared within
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 Table 2. Clinical Characteristics of the Study Population by Burn Scar Type a

PS Types
Odds Ratio
Overall Study NS HS HS ⴙ C C AS (95% CI),
Characteristic b Population (n=1058) (n=905) (n=385) (n=88) (n=4) PS vs NS c
Sex
Male 1526 (63) 692 (65) 551 (61) 227 (59) 53 (60) 3 (75) 1.00 [Reference]
Female 914 (37) 366 (35) 354 (39) 158 (41) 35 (40) 1 (25) 1.24 (0.99-1.56)
Age at burn, median (IQR), y (n=2408) 38 (25-54) 38 (25-54) 38 (24-54) 36 (24-52) 41 (22-59) 31 (15-51) 0.94 (0.81-1.10)
BSA, median (IQR), % 20 (10-35) 18 (10-35) 20 (10-35) 30 (15-45) 15 (10-30) 10 (8-14) 1.15 (0.97-1.36)
FT BSA, median (IQR), % 10 (0-25) 8 (0-20) 10 (4-20) 20 (10-30) 10 (5-25) 10 (7-11) 1.54 (1.22-1.94)
Cause of burn (n=2234)
Chemical 50 (2) 22 (2) 21 (3) 5 (1) 1 (1) 1 (50) 0.91 (0.43-1.95)
Contact 36 (2) 18 (2) 10 (1) 6 (2) 2 (3) 0 0.72 (0.27-1.91)
Electrical 36 (2) 29 (3) 6 (1) 0 1 (1) 0 0.17 (0.06-0.49)
Flame 1486 (67) 620 (64) 561 (67) 262 (76) 43 (58) 0 1.00 [Reference]
Scald 297 (13) 140 (14) 125 (15) 18 (5) 14 (19) 0 0.80 (0.59-1.10)
Pressure 5 (⬍1) 0 3 (⬍1) 2 (1) 0 0 NA
Flash 299 (13) 128 (13) 104 (12) 54 (16) 13 (18) 0 0.96 (0.65-1.41)
Sunburn 12 (1) 10 (1) 2 (⬍1) 0 0 0 0.14 (0.04-0.58)
Steam 13 (1) 6 (1) 6 (1) 0 0 1 (50) 0.84 (0.20-3.49)
Anatomic burn site
Abdomen 170 (7) 98 (9) 67 (7) 5 (1) 0 0 0.41 (0.30-0.58)
Lower limb 606 (25) 234 (22) 321 (35) 48 (12) 1 (1) 2 (50) 0.90 (0.70-1.16)
Upper limb 834 (34) 301 (28) 308 (34) 185 (48) 39 (44) 1 (25) 1.00 [Reference]
Neck 162 (7) 71 (7) 26 (3) 49 (13) 16 (18) 0 0.72 (0.51-1.03)
Perineum 77 (3) 50 (5) 24 (3) 3 (1) 0 0 0.30 (0.19-0.50)
Head 290 (12) 199 (19) 61 (7) 20 (5) 9 (10) 1 (25) 0.26 (0.19-0.34)
Chest 301 (12) 105 (10) 98 (11) 75 (19) 23 (26) 0 1.05 (0.80-1.39)
Burn treatment
Medical 1106 (45) 678 (64) 336 (37) 65 (17) 25 (28) 2 (50) 0.25 (0.20-0.31)
Surgical 1334 (55) 380 (36) 569 (63) 320 (83) 63 (72) 2 (50) 1.00 [Reference]
No. of surgical procedures (n=2301) 2.10 (1.73-2.56) d
0 1105 (48) 677 (67) 336 (39) 65 (18) 25 (32) 2 (50)
1 830 (36) 256 (25) 373 (43) 168 (48) 31 (40) 2 (50)
2 223 (10) 44 (4) 99 (12) 67 (19) 13 (17) 0
3 87 (4) 15 (1) 35 (4) 31 (9) 6 (8) 0
4 29 (1) 5 (⬍1) 12 (1) 10 (3) 2 (3) 0
5 21 (1) 7 (1) 5 (1) 9 (3) 0 0
6 6 (⬍1) 3 (⬍1) 0 3 (1) 0 0
Type of surgical approach (n=1330)
Alexander 15 (1) 4 (1) 7 (1) 4 (1) 0 0 1.05 (0.13-8.83)
Dermal abrasion 34 (3) 14 (4) 14 (2) 4 (1) 2 (3) 0 0.55 (0.26-1.16)
Flap 6 (⬍1) 6 (2) 0 0 0 0 NA
Excision 43 (3) 7 (2) 23 (4) 12 (4) 1 (2) 0 1.97 (0.82-4.69)
Excision and autograft 1211 (91) 335 (89) 515 (91) 299 (93) 60 (95) 2 (100) 1.00 [Reference]
Excision and xenograft 6 (⬍1) 5 (1) 1 (⬍1) 0 0 0 NA
Excision and allograft 15 (1) 7 (2) 7 (1) 1 (⬍1) 0 0 NA
Type of skin graft (n=847)
1:2 229 (27) 59 (27) 114 (30) 44 (21) 12 (31) NA 0.97 (0.60-1.55)
1:4 450 (53) 113 (51) 218 (58) 108 (51) 11 (28) NA 1.00 [Reference]
1:6 8 (1) 3 (1) 2 (1) 3 (1) 0 NA 0.56 (0.12-2.51)
Sheet 160 (19) 47 (21) 40 (11) 57 (27) 16 (41) NA 0.81 (0.49-1.33)
Wound healing time, median (IQR), 40 (25-67) 33 (20-60) 40 (27-62) 55 (35-87) 57 (31-100) 19 (10-28) 1.15 (1.02-1.29)
d e (n=2367)
Excision and grafting timing, median 10 (5-17) 10 (5-19) 10 (6-17) 7 (3-16) 10 (4-16) 9 0.90 (0.79-1.02)
(IQR), d f (n=1102)

Abbreviations: AS, atrophic scars; BSA, burn surface area; C, contractures; CI, confidence interval; FT, full thickness; HS, hypertrophic scars; IQR, interquartile
range; NA, not applicable; NS, normotrophic scars; PS, pathologic scars.
a Unless otherwise indicated, data are reported as number (percentage) of patients.
b Unless otherwise indicated, the total number of patients included in the analysis of a given group is 2440.
c Unless otherwise indicated, odds ratios apply (1) to the effect of an interquartile difference for continuous variables (eg, age interquartile difference, 29 years;
therefore, for every increase of 29 years in age, the odds ratio is 0.94) or (2) to the category with the highest observed frequency (reference) for categorical
variables (eg, male sex is the highest observed category; therefore, the 1.24 odds ratio is interpreted for female vs male). Boldface type indicates a statistically
significant finding.
d Odds ratio applies to the effect of difference in 1 surgical procedure.
e From burn trauma to complete reepithelialization.
f From burn trauma to the first surgical procedure.

a few weeks. On the contrary, pathologic scars (hypertrophy, scars, and the checkups were repeated every 30 to 40 days. When
hypertrophy with contracture, contracture, and/or atrophy) were scarring began to enter into the remission phase, clinical con-
diagnosed on the basis of the presence of typical signs and symp- trols were reduced to every 2 months, followed by every 6
toms (Table 3). Medical treatment was started for pathologic months after complete remission.

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1 1
2 2
4 4
3 3 3 3
5 5
6 6
7 7 7 7
Front Back
Figure 1. Scheme for acquisition data of burn locations. For analysis,
anatomic burn sites were characterized as (1) head, including the face and
scalp; (2) neck, including the nape; (3) upper limb, including the upper arms,
elbows, forearms, wrists, hands, and fingers; (4) chest, including the
shoulders, armpits, breasts, and thoracic back; (5) abdomen, including the
abdominal wall and lumbar back; (6) perineum, including the genitalia, groin,
and gluteal and anal region; and (7) lower limb, including the thigh, knee,
lower legs, ankles, feet, and toes.
In the case of hypertrophy, the diffusion (localized or gen-
eralized) was evaluated. To evaluate the hypertrophic scar evo-
lution, we considered (1) the type of treatment applied to ev-
ery location (medical and/or surgical), (2) latency of appearance
(from total reepithelialization), (3) activity duration (from in-
duction to initial remission), (4) remission time (from initial
remission to complete remission), and (5) total duration of hy-
pertrophic scarring (from induction to complete remission).
For contracted scars, only the latency of appearance and type
of treatment were considered.
Surgical indications included scar retraction or hypertrophic
scarring associated with contractures that could not be managed
by the conventional use of physiotherapeutic rehabilitation. While
surgery was indicated for hypertrophy, it was used only in the
case of stable scars, ie, those in complete remission.20
Continuous data are expressed as medians with interquartile
ranges (IQRs) as a measure of variability. Scar evolution was ex-
pressed by the time before the onset of scarring and was esti-
mated using the Kaplan-Meier curve and 95% confidence inter-
val (CI).
The individual effects of patient characteristics and clinical and
instrumental variables on the risk of pathologic postburn scar-
ring (vs normotrophic scarring) were evaluated by a logistic re-
gression model and a univariate estimate of the odds ratios (ORs)
presented along with their 95% CIs. No P values are presented.
The same approach was used for evaluating the risk of a patho-
logic scar developing into a hypertrophic or contracted state. As
the analysis was performed at a “scar” level, the Huber-White es-
timator21 was used to adjust for the correlation between the mul-
tiple observations contributed by the same patient. All variables
considered were entered into the model “as is” without any trans-
formation or cutting off. The nonlinear effect of covariates was
modeled using a restrictive cubic spline function, and its signifi-
cance was assessed by the Wald ␹2 test.
The model strategy was determined following a rigid model
selection strategy, which was based on clinical discussion and
statistical selection procedures. The best fitting model was cho-
sen on the basis of the Akaike information criterion that was
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Table 3. Clinical Presentation of Pathologic Postburn Scars
Scar Clinical Characteristics
Scar Type Signs Symptoms
Hypertrophy a Raised, erythematous, Pain, itching, dysesthesias
or fibrous skin
Contracture Skin coarctation or Reduced range of motion
deformity in involved joints,
subjective sensation of
constriction
Atrophy Thinned or fragile skin Itching
a Induction characterized by the onset of the listed signs and symptoms
and remission by a gradual decrease in intensity.
applied backward (ie, starting from a model with all relevant
variables and eliminating those that were not significant) at a
significance level of .05. Interaction among variables was checked
in a similar way. Finally, a multivariate model was built and
evaluated using a graphical examination of residual diagnos-
tics. Discrimination Index D (the higher the better) and the
Somer concordance index Dxy (the closer to 1 in absolute value
the better) were obtained and formed the main pillar of the sta-
tistical model predictive accuracy evaluation.
A nomogram was then produced to report the findings of
the multivariate model in a more suitable manner to allow for
its application in daily clinical practice. In the absence of an
external data source, to account for the degree of optimism in
model accuracy evaluations induced by the use of the same data
source for training and testing purposes, all goodness of fit in-
dexes were computed using cross-validation and bootstrap (1000
runs). The S-Plus statistical package (2000 release) and the Har-
rells Design and Hmisc libraries were used for analysis (In-
sightful Corporation, Seattle, Washington).
RESULTS
The clinical characteristics of the study population are
summarized in Table 2.
BURN SCAR CHARACTERISTICS
A total of 540 of 703 patients were classified as having
pathologic scars, for an overall prevalence of 77%. The
development of hypertrophy was observed in 310 (44%)
(Figure 2A-C), hypertrophy with contracture in 196
(28%) (Figure 2B), and pure contracture in 24 (5%)
(Figure 2D). A localized form of hypertrophic scarring
was observed in 372 (69%), while scarring was general-
ized to all burn locations in 168 (31%).
The prevalence of pathologic scarring decreased to 57%
when the cohort was considered according to the anatomic
burn sites (1382 of 2440). However, hypertrophy with and
without contracture remained the most common type of scar
(28% [385 of 1382] and 65% [905 of 1382], respectively).
As to scar evolution, 403 of 506 burn patients with hy-
pertrophic scars (80%) completed the surveillance pro-
gram, with 986 of 1290 hypertrophic scar areas healed
(77%) (ie, with complete remission of clinical signs of scar
abnormality), 199 lost to follow-up (16%), and 105 still
in evolution (8%) at the end of the study (May 15, 2006).
The percentage of hypertrophic scars increased, with
a median latency of 23 days (IQR, 11-45 days) from com-
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 A B
C D
Figure 2. Scar types and evolution phases. A, Hypertrophic scar in active phase on the dorsal surface of the hand; B, hypertrophic scar in active phase on the back, with
contracted scar on posterior armpit pillar; C, hypertrophic scar in remission phase on the right shoulder and arm; D, isolated contracture scar on the neck.
plete burn healing. The total median length of the scar
process was 15 months (IQR, 10-23 months) divided into
an activity phase of 23 weeks (IQR, 15-36 weeks) and a
remission phase of 40 weeks (IQR, 24-67 weeks)
(Table 4).
When stratified according to the Muir classification
chart,19 153 hypertrophic scars regressed within 1 year
and were considered to undergo short-term evolution
(38%). The same percentage became normotrophic within
2 years (intermediate-term evolution), and 98 remained
active for many years (24%) (long-term evolution)
(Table 4). When the cohort was evaluated according to
the anatomic scar areas, the percentages were similar to
those found in the Muir scar classification analysis
(Figure 3). The remission period could be considered
the crucial phase for the classification of the evolution
term because it lasted for a median period of 5 months
(IQR, 3.5-6.5 months) in short-term scars, 10.5 months
(IQR, 8-13 months) in intermediate-term scars, and 23
months (IQR, 18-29 months) in long-term scars. On the
contrary, the median length of the activity phase was quite
similar in all 3 different evolution types (6 months; IQR,
4-8 months) (Table 4).
Hypertrophic scars with contracture developed ear-
lier than did pure hypertrophic scars (19 days [IQR, 10-34
days] vs 26 days [IQR, 12-50 days]), and a median of 2
months more was required to reach complete remission
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(16 months [IQR, 11-24 months] vs 14 months [IQR,
10-23 months]).
RISK FACTOR ANALYSIS
A univariate analysis of predictors of postburn patho-
logic scarring is summarized in Table 2, while a univari-
ate analysis of the predictors of postburn hypertrophic
scarring and postburn contracted scarring is summa-
rized in Table 5.
SEX AND AGE AT BURN TRAUMA
The study population was made up of 412 men (59%) and
291 women (41%). As summarized in Table 2, women were
more prone to postburn pathologic scarring than men (OR,
1.24; 95% CI, 0.99-1.56). The median age at initial burn
injury was 38 years (IQR, 25-54 years). Older subjects had
a significantly lower risk of pathologic scarring (OR, 0.64;
95% CI, 0.45-0.90), both for hypertrophy (OR, 0.55; 95%
CI, 0.36-0.82) and for contracture (OR, 0.68; 95% CI, 0.44-
1.05) at multivariate analysis (Table 6).
BURN SEVERITY
The median BSA was 18% (IQR, 10%-35%) in patients
with normotrophic scars, while it was 30% (IQR, 15%-
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 Table 4. Clinical Characteristics of Hypertrophic Scar Evolution a

Latency of Activity Remission Total Duration of Follow-up

Scar Characteristic Appearance Time Time Scar Evolution Time b
Hypertrophic (n = 905) 26 (12-50) 156 (98-245) 269 (157-463) 421 (296-695) 469 (337-755)
Hypertrophic with contracture (n=385) 19 (10-34) 182 (123-273) 295 (178-471) 476 (341-727) 506 (370-777)
Contracture (n = 88) 27 (10-55) NA NA NA NA
Short term (n = 368) 26 (13-48) 114 (80-152) 151 (98-196) 275 (212-333) 316 (252-366)
Intermediate term (n=389) 24 (10-43) 182 (126-245) 322 (235-392) 499 (421-595) 529 (454-639)
Long term (n = 229) 19 (11-37) 231 (154-408) 699 (556-875) 961 (839-1188) 1003 (878-1212)
Study population (n=986) 23 (11-45) 162 (105-251) 280 (166-469) 447 (315-702) 483 (349-759)

Abbreviation: NA, not applicable.

a Data are expressed in days as median (interquartile range).
b From complete reepithelialization to complete hypertrophic scar remission.

BURN LOCATION
100

90 More than 50% of the 2440 burn sites involved the 4 limbs,
80 with the upper limbs being the most commonly injured
70 area (34%). Distal segments of affected anatomic sites were
Still in Evolution, %

60 the most involved (eg, wrist and hand), especially in as-

50
40
30
20
10
0 Of the 834 burns of the upper limb and of the 301 chest
0 500 1000 1500
Time, d
Figure 3. Kaplan-Meier curve of hypertrophic scar evolution (solid line) with
95% confidence limits (dotted lines).
45%) in those burn patients who developed hypertrophic-
contracted scars. The same difference was observed in
the full-thickness BSA analysis: 8% (IQR, 0%-20%) for
patients without pathologic scars and 20% (IQR, 10%-
30%) for those with hypertrophy and contracture. The
risk of postburn pathologic scarring was significantly
higher among those with a high percentage of BSA (OR,
1.15; 95% CI, 0.97-1.36) and full-thickness BSA (OR, 1.54;
95% CI, 1.22-1.94).
BURN CAUSE
The prevailing burn cause was the flame, primed most
commonly by alcohol, gasoline, or solvents. Scalds (preva-
lently by hot water) were the second most frequent cause,
followed by flash flame caused usually by flammable gases.
Less common among the evaluated burns were electri-
cal burns, chemical burns (usually by acids), contact
burns, steam burns, pressure burns, and sunburns. A total
of 620 of the 1058 normotrophic scar areas were caused
by flame burns (64%) compared with 262 of the 385 hy-
pertrophic-contracted scar areas (76%). Compared with
flame burns, electrical burns (OR, 0.17; 95% CI, 0.06-
0.49) and sunburns (OR, 0.14; 95% CI, 0.04-0.58) were
significantly more likely to result in normotrophic scar-
ring, while scalds had significantly less risk for con-
tracted scarring (OR, 0.46; 95% CI, 0.27-0.80).
sociation with head burns (12%), which were mainly on
the nose, ears, and the cheeks.
Burns on the abdomen (OR, 0.41; 95% CI, 0.30-
0.58), perineum (OR, 0.30; 95% CI, 0.19-0.50), and head
(OR, 0.26; 95% CI, 0.19-0.34) had a significantly lower
risk of pathologic scarring than burns of the upper limb.
2000 2500 3000
burns, respectively, 533 (64%) and 196 (65%) gener-
ated pathologic scars. Burns of the lower limb often
generated hypertrophic scars (OR, 1.34; 95% CI, 1.03-
1.74) rather than contractures (OR, 0.28; 95% CI, 0.18-
0.44). In contrast, burns on the neck generated more
hypertrophic and contracted scars than they did pure hy-
pertrophy (OR, 0.36; 95% CI, 0.22-0.58).
BURN TREATMENT
The aim of this study was not to evaluate the efficacy
of one specific burn treatment over another on the
scar outcome. The strategies applied were not selected
before starting but rather followed those standard
indications that had produced the most evidence in lit-
erature. Therefore, the associations obtained were the
result of a simple retrospective observation of the
study cohort.
Surgical indications were present for 1334 burn sites
(55%). It was necessary to perform 2 or more surgical
procedures in 31% of the surgical burns (366 of 1196),
commonly in massive burns for multiple excisions and
in deep burns for temporary coverage with alloplastic skin
grafts to prepare the wound bed. When burn surgery was
evaluated, only the last operation was taken into con-
sideration as a presumed risk factor.
The type of surgical approach most commonly used
was excision and coverage with autologous skin grafts
(91%; 1211 of 1330). The most common type of skin
graft applied was 1:4 meshed (53%), while the sheet skin
graft was used in 78% of neck burns and in 26% of up-
per limb burns, particularly for those on the dorsal sur-

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 face of fingers and hands. Dermal abrasion was used most
frequently in the treatment of head burns (3%; 34 of 1330), Table 5. Univariate Analysis of Predictor Characteristics
while local and regional flaps were used for the cover- for Hypertrophy and Contracture
age of deep electrical necrosis (6 of 1330).
Odds Ratio (95% CI) a
Nonsurgical burn healing was significantly more pro-
tective in terms of scar outcome than surgical burn treat- Hypertrophy vs Contracture vs
ment (OR, 0.25; 95% CI, 0.20-0.31). In fact, the risk of Predictor Characteristic Normotrophy Normotrophy
pathologic scarring significantly doubled for every sur- Female sex (vs male) 1.21 (0.94-1.57) 1.30 (0.96-1.77)
gical operation performed (OR, 2.2; 95% CI, 1.73- Age (IQD, 29 y) 0.95 (0.79-1.13) 0.93 (0.76-1.14)
2.56). No substantial difference was evidenced by the BSA (IQD, 25%) 0.95 (0.78-1.16) 1.53 (1.27-1.85)
analysis of the type of surgical technique used. FT BSA (IQD 25%) 2.48 (1.80-3.41) 5.76 (3.77-8.79)
Burn cause
More interesting were the results obtained from skin Flame 1.00 [Reference 1.00 [Reference
grafting analysis. Sheet skin grafts were significantly less Chemical 1.05 (0.47-2.38) 0.55 (0.18-1.67)
prone to hypertrophic scarring (OR, 0.44; 95% CI, 0.25- Contact 0.61 (0.19-1.95) 0.90 (0.32-2.55)
0.78) and more prone to contracture, although not sig- Electrical 0.23 (0.08-0.65) 0.07 (0.01-0.52)
nificantly (OR, 1.47; 95% CI, 0.85-2.56) than 1:4 meshed Scald 0.99 (0.70-1.39) 0.46 (0.27-0.80)
skin grafts. Pressure NA NA
Flash 0.90 (0.56-1.43) 1.06 (0.69-1.65)
Finally, a delayed wound healing time was a signifi-
Sunburn 0.22 (0.05-0.89) NA
cant risk factor for pathologic scarring (OR, 1.15; 95% Steam 1.11 (0.25-4.80) NA
CI, 1.02-1.29), especially for contractures (OR, 1.40; 95% Burn anatomic site
CI, 1.16-1.68). Surprisingly, an early excision and graft Upper limb 1.00 [Reference 1.00 [Reference
timing did not seem to influence the final scar outcome. Abdomen 0.67 (0.48-0.94) 0.07 (0.03-0.17)
Lower limb 1.34 (1.03-1.74) 0.28 (0.18-0.44)
Neck 0.36 (0.22-0.58) 1.23 (0.83-1.82)
POSTBURN SCAR TREATMENT
Perineum 0.47 (0.28-0.79) 0.08 (0.02-0.26)
Head 0.30 (0.22-0.41) 0.20 (0.13-0.30)
Seventy-nine percent of all pathologic postburn scar lo- Chest 0.91 (0.67-1.25) 1.25 (0.91-1.73)
cations were treated with medical and rehabilitative Surgical (reference) vs medical 3.02 (2.40-3.81) 1.40 (1.16-1.68)
therapy (1097 of 1382): 82% of hypertrophic scars treatment
(n=742), 35% of pure contractures (n = 31), and 84% of Number of surgical procedures b 1.74 (1.43-2.13) 2.46 (1.94-3.12)
Type of surgical approach
hypertrophic and contracted scars (n=324). On the con-
Excision and autograft 1.00 [Reference 1.00 [Reference
trary, there were indications for reconstructive surgery Alexander 1.14 (0.13-9.69) 0.23 (0.08-11.29)
in 233 of 1382 pathologic scar locations (17%). Dermal abrasion 0.65 (0.29-1.47) 0.40 (0.15-1.07)
The most commonly prescribed therapy was a com- Flap NA NA
pressive elastic garment (46%), especially for limb and Excision 2.14 (0.86-5.32) 1.73 (0.60-4.99)
chest scars. Contact media (20%), represented by sili- Excision and xenograft 0.13 (0.01-1.35) NA
cone gel sheeting and adhesive microporous hypoaller- Excision and allograft 0.65 (0.12-3.51) 0.13 (0.05-0.38)
Type of skin graft
genic paper tape, were used on scars of limited exten- 1:4 1.00 [Reference 1.00 [Reference
sion, often in partial remission and sometimes in 1:2 1.00 (0.59-1.70) 0.90 (0.85-2.56)
association with pressure therapy. Other treatment in- 1:6 0.35 (0.04-2.66) 0.95 (0.19-4.81)
cluded rehabilitation (17%), thermal cures and mas- Sheet 0.44 (0.25-0.78) 1.47 (0.85-2.56)
sages (10%), splints, LPG System Bodywear (Valencia, Wound healing time 1.02 (0.92-1.14) 1.40 (1.16-1.68)
France), laser therapy, and corticosteroid injections. (IQD, 42 d)
Excision and grafting timing 0.93 (0.80-1.08) 0.80 (0.66-0.96)
Surgical treatment was indicated mainly for con- (IQD, 12 d)
tracted scars (87%; 196 of 233). Multiple reconstructive
procedures were often necessary to obtain a complete cor- Abbreviations: BSA, burn surface area; CI, confidence interval; FT, full
rection of skin coarctation. Hypertrophic scars were al- thickness; IQD, interquartile difference; NA, not applicable.
a Unless otherwise indicated, odds ratios apply (1) to the effect of an IQD
ways operated on after complete remission and mainly
for continuous variables (eg, age IQD, 29 years; therefore, for every increase
for aesthetic reasons (4%; 37 of 1058). The most com- of 29 years in age, the odds ratio for hypertrophy vs normotrophy is 0.95) or
monly corrected scar sites were the neck, hand, mouth, (2) to the category with the highest observed frequency (reference) for
eyelid, elbow, and axilla. categorical variables (eg, male sex is the highest observed category;
therefore, the 1.21 odds ratio for hypertrophy vs normotrophy is interpreted
Surprisingly, medical treatment did not significantly for female vs male). Boldface type indicates a statistically significant finding.
improve time to complete remission (hazard ratio, 0.79; b Odds ratios apply to the effect of difference in 1 surgical procedure.
95% CI, 0.57-1.11).

PREDICTION OF OUTCOME considered as single outcomes, the addition of full-

Multivariate analysis results based on each prognostic
model are summarized in Table 6.
Sex, age, anatomic burn site, number of surgical pro-
cedures, and type of skin graft were selected as indepen-
dent predictors of pathologic postburn scarring. How-
ever, when hypertrophic and contracture scarring were
thickness BSA to the other variables was significantly as-
sociated with scar outcome.
Finally, to estimate the risk of developing a pathologic
postburn scar in the individual patient, a nomogram was
generated (Figure 4). On the basis of the multivariate
model for pathologic scarring, specific points relative to the
effect on the risk of the categorical variables were as-

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 Table 6. The Results of the Multivariable Analysis of Predictor Characteristics a

Postburn Scarring Odds Ratio (95% CI) b

Predictor Characteristic Pathologic Hypertrophic Contracture

Female sex (vs male) 1.28 (0.82-2.00) 1.20 (0.74-1.93) 1.21 (0.66-2.22)
Age (IQD 29 y) 0.64 (0.45-0.90) 0.55 (0.36-0.82) 0.68 (0.44-1.05)
FT BSA (IQD 25%) 0.63 (0.43-0.94) 1.62 (0.95-2.77)
Burn anatomic site
Upper limb 1.00 [Reference 1.00 [Reference 1.00 [Reference
Abdomen 0.18 (0.10-0.32) 0.35 (0.19-0.62) 0.02 (0.00-0.10)
Lower limb 0.66 (0.40-1.11) 1.26 (0.73-2.18) 0.16 (0.08-0.35)
Neck 3.27 (1.01-10.54) 1.06 (0.22-5.06) 5.10 (1.45-17.69)
Perineum 0.16 (0.06-0.39) 0.33 (0.13-0.81) 0.03 (0.00-0.23)
Head 0.82 (0.26-2.60) 0.95 (0.23-3.83) 0.69 (0.17-2.85)
Chest 0.80 (0.45-1.41) 0.61 (0.32-1.16) 1.06 (0.55-1.98)
No. of surgical procedures c 1.10 (0.87-1.39) 0.99 (0.76-1.29) 1.39 (1.06-1.82)
Type of skin graft
1:4 1.00 [Reference 1.00 [Reference 1.00 [Reference
1:2 0.95 (0.57-1.59) 1.06 (0.62-1.84) 0.71 (0.36-1.37)
1:6 0.42 (0.07-2.57) 0.24 (0.02-2.60) 0.60 (0.05-7.47)
Sheet 0.47 (0.26-0.84) 0.28 (0.15-0.54) 0.84 (0.39-1.79)

Abbreviations: CI, confidence interval; FT BSA, full-thickness burn surface area; IQD, interquartile difference.
a For pathologic postburn scars altogether, D and Dxy were 0.05 and 0.30, respectively. When hypertrophy and contracture were considered separately, D and
Dxy became 0.06 and 0.30 for the first model and 0.24 and 0.55 for the second model.
b Unless otherwise indicated, odds ratios apply (1) to the effect of an IQD for continuous variables (eg, age IQD, 29 years; therefore, for every increase of 29
years in age, the odds ratio for pathologic postburn scarring is 0.64) or (2) to the category with the highest observed frequency (reference) for categorical
variables (eg, male sex is the highest observed category; therefore, the 1.28 odds ratio for pathologic postburn scarring is interpreted for female vs male).
Boldface type indicates a statistically significant finding.
c Odds ratios apply to the effect of difference in 1 surgical procedure.

Points 0 10 20 30 40 50 60 70 80 90 100

Female
Sex
Male

Age, y 100 90 80 70 60 50 40 30 20 10 0
Upper limb
Abdomen Chest
Burn site Perineum Lower limb Neck

Head
1 3 5
Surgical procedures, No.
0 2 4 6

Sheet 1:4
Type of skin graft
1:2

Total points 0 20 40 60 80 100 120 140 160 180 200

Risk for pathologic postburn scarring, % 20 30 40 50 60 70 80 90 95

Figure 4. Nomogram for estimating patient’s risk for pathologic postburn scarring.

signed. The patient’s values on each predictor are located, COMMENT

and a line is drawn upward to determine how many points
the patient receives for each variable value. A point scale
was used for the continuous variable. Thus the points are
summed, and the result is located on the “total points” axis.
A line is drawn downward to then determine the risk of
developing a pathologic postburn scar.
Scar formation is the natural final step of wound heal-
ing. The problem of pathologic scarring is severe for pa-
tients and difficult for clinicians, especially in the case
of burn injuries, because no reliable satisfactory meth-

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 ods exist for its alleviation.10 Therefore, experts recom-
mend22 that follow-up treatment of burn patients be car-
ried out by the highly specialized medical personnel in
outpatient clinics located within burn centers.
Following the maxim that prevention of complica-
tions is preferable to treatment of an established prob-
lem,22 burn care specialists are searching for clinical cri-
teria to identify patients who might benefit from
prophylactic programs. To our knowledge, the present
study is the first to investigate risk prediction models for
pathologic postburn scarring. Indeed, the data analyzed
herein probably represent the largest cohort published
on this open question.
These data show that postburn pathologic scarring is
extremely common (a prevalence of 77%) and that hy-
pertrophy and contracture should be classified sepa-
rately if we are to understand these phenomena better.
Hypertrophy is the most frequently encountered patho-
logic feature, either alone (44%) or in combination with
contracture (28%) at the same time in the same patient.
Moreover, it was observed that most patients who de-
veloped a pathologic scar in 1 anatomic area had nor-
motrophic outcomes in other burn sites (69% had local-
ized diffusion of hypertrophy).
Hypertrophic scars had an early appearance from com-
plete reepithelialization (3.5 weeks; IQR, 1.5-6.5)
(Table 4), reaching at least a steady state after an initial
activation phase followed by a regression phase (total du-
ration, 15 months). The remission phase persisted for long
periods but varied considerably from individual to indi-
vidual. Consequently, remission might be considered the
most important period on which the research should be
focused. Five percent of the cohort had pure contrac-
tures, which were usually diagnosed late owing to their
having a longer latency period of manifestation (27 days;
IQR, 10-55 days). Atrophy is rare (4 of 2440 anatomic
burn sites), and it could be considered, especially in older
subjects, a late outcome of different types of scars that
finally evolve into areas of poor extracellular matrix syn-
thesis. The epidemiologic data confirm the classifica-
tion charts proposed by Magliacani et al18 and Muir19 as
reliable stratification methods.
Noteworthy are the data on sex, age, anatomic burn
site, number of surgical procedures, and type of skin graft
that allow for a significant prediction of postburn patho-
logic scarring. Moreover, they provide additional prog-
nostic information and indicate interesting direction for
biological research.
Concerning the causes of postburn pathologic scar-
ring, it has been hypothesized that hypertrophy is a sys-
temic inflammatory disease of central origin, regulated
by local influencing factors.23 Indeed some results of the
present study seem consistent with this hypothesis. Nu-
merous studies have pointed out the key role played by
lymphocytes and the skin’s immune system in general
in the maintenance of a continuous inflammatory acti-
vated state of hypertrophic tissue.24-26
Our data seem to support the role of the immune sys-
tem for a number of reasons. First, female sex carries a higher
risk for pathologic postburn scarring, as it does for most
diseases of immunologic pathogenesis (eg, rheumatoid ar-
thritis, Sjögren syndrome, and systemic lupus erythema-
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tosus).27 Second, burn patients who presented with patho-
logic scars were significantly younger than those with
normotrophic scarring. Organs and systems, particularly
the immune system, are less functional in older persons,
in whom autoimmune diseases have hazy and insidious
signs and symptoms. On the contrary, children have a strong
anabolic basal activity that often generates an unbalance
in the remodeling phase of wound healing.28
Finally, according to the results obtained from our analy-
sis of burn severity, it is also likely that hormonal context
(eg, stress index) during the acute phase of burns could
play a role in scar alterations. In fact, a positive correlation
has been noted between the levels of serum inflammatory
molecules (eg, prolactin and cytokines) at early time points
and burn severity as expressed by BSA.29 Indeed this cor-
relation suggests that burn injury mediates a systemic re-
sponse, independent from the site, continuing from the
acute to the postburn phase,30 as demonstrated in the mul-
ticenter study of the genomic and proteomic response to
burn injury.31 While our findings are not evidence based,
our analysis of the recommended medical topical treat-
ment of scars indicates that pressure garments and sili-
cone gel sheeting22 could help to alleviate symptoms and
improve body homeostasis. However, there is no clear evi-
dence that these local aids influence either scar evolution
or the need for secondary scar correction, further support-
ing the idea that hypertrophic scars are sustained by a sys-
temic inflammatory mechanism.
As to local variables, the role of the single anatomic
site has a strong risk-prediction significance, thus being
implicated in the pathogenesis of pathologic scarring. The
neck and upper limb are sites at higher risk than the ab-
domen and perineum. Surely each specific region has dif-
ferent histomorphologic characteristics that could be cru-
cial in the wound healing processes.32 Interestingly, it has
been suggested that hypertrophic scars occur in sites char-
acterized by cones, localized in the deep dermis and con-
taining skin appendages and fat domes that perforate the
dermis matrix.33 Moreover, an imbalance in skin ten-
sion after healing could give rise to contractures. In-
deed, it has been observed that myofibroblasts in these
scars fail to undergo apoptosis because there are incor-
rect stimulations.34,35
When dealing with the role of burn treatment and its
efficacy on the scar outcome, a burn without surgical in-
dications might be reasonably defined as superficial or
of moderate partial thickness. The analysis of surgical burn
treatment emphasizes that burn depth is an important
risk factor: destruction of the dermal or hypodermal layer
could create serious repair problems, which may often
induce pathologic scarring. The type of skin graft is also
significant, with sheet skin grafts being more protective
than other types from the risk of pathologic scarring. It
has been suggested that the sheet skin graft bears new
epithelium and new dermal fibroblasts, while with meshed
skin grafts, the healing process is also sustained by the
fibroblasts coming from the injured area, which have a
profibrotic phenotypic pattern.36
In addition, a delay in reepithelialization increases the
risk of wound infection and prolongs the inflammatory
phase, consequently leading to scar abnormalities.37 A less
important role seems to be played by the surgical tech-
WWW.ARCHFACIAL.COM
 niques used to resurface third-degree burns. Moreover, new
biological or biosynthetic cutaneous substitutes have of-
fered promising improvement in scar quality, although their
role should be investigated in large case series.17,38
On the whole, the results of the present study may have
relevant clinical implications and could be used to im-
prove the approach to postburn pathologic scars, in par-
ticular in view of the findings from the multivariate analy-
sis and its use through the application of a nomogram
(Figure 4). Risk information may be easily integrated into
routine clinical practice for early risk stratification, thus fa-
cilitating optimal medical prevention and helping physi-
cians adopt follow-up timing and more aggressive or ex-
perimental therapies for subjects likely to be at high risk.
We would welcome the validation of our prediction
model in other cohorts worldwide to provide us the op-
portunity to adjust for any variations found and thus set
up a risk-prediction instrument that might easily be ap-
plied to most situations with a high degree of accuracy.
Accepted for Publication: June 26, 2007.
Correspondence: Ezio Nicola Gangemi, MD, Depart-
ment of Plastic and Reconstructive Surgery–Burn Cen-
ter, Traumatological Center, Via Zuretti 29, 10126 Turin,
Italy (ezio.nicola@tele2.it).
Author Contributions: Drs Gangemi and Stella had full
access to all the data in the study and take responsibility
for the integrity of the data and accuracy of the data analy-
sis. Study concept and design: Gangemi and Stella. Acqui-
sition of data: Gangemi, Zingarelli, Cairo, Bollero, Ganem,
Capocelli, Cuccuru, Cassano, Risso, and Stella. Analysis
and interpretation of data: Gangemi, Gregori, Berchialla,
and Stella. Drafting of the manuscript: Gangemi, Gregori,
Zingarelli, Cairo, Bollero, Ganem, Capocelli, Cuccuru,
Cassano, Risso, and Stella. Critical revision of the manu-
script for important intellectual content: Gangemi, Gregori,
Berchialla, and Stella. Statistical analysis: Gregori and
Berchialla. Administrative, technical, and material sup-
port: Zingarelli, Cairo, Bollero, Ganem, Capocelli,
Cuccuru, Cassano, and Risso. Study supervision: Stella.
Financial Disclosure: None reported.
Previous Presentation: This article was presented at the
13th International Society for Burn Injuries Congress; Sep-
tember 25, 2006; Fortaleza, Brazil.
Additional Contributions: Simone Teich Alasia, MD, pro-
vided continuing support and collaboration.
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