Annals of Burns and Fire Disasters - vol. X - n.

2 - June 1997
POST-BURN PATHOLOGICAL SCAR: CLINICAL ASPECTS AND
THERAPEUTIC APPROACH
MagIiacani G.,(1) SteIIa M.,(1) CastagnoIi C.,(1) Trombotto (2) Ondei S.(2) CaIcagni M.(1)
(1) Department of PIastic Surgery and Burn Unit, Trauma Centre, Turin, ItaIy
(2) Centre for Immunogenetics and ExperimentaI OncoIogy, NationaI Research CounciI, ItaIy

SUMMARY. Pathological scarring continues to represents a major challenge Ior reconstructive surgeons. its
anatomopathological classiIication is poorly deIined and the relative epidemiological data are controversial.
Our research group has thereIore drawn up a classiIication chart on the basis oI the morphological aspects oI
pathological scars. Hypertrophic scarring, the burn sequela most Irequently observed in our case records, is
characterized by the onset oI typical clinical Ieatures which aIter a variable time course oI activation undergo a
phase oI remission. The Iactors that produce this progressive radical change in the scars are not clear. It has
recently been suggested that immunological Iactors may play a major role in the pathogenesis oI hypertrophic
scars. In order to have a better understanding oI the pathophysiological Iactors involved, we studied active
hypertrophic scars by means oI immunohistochemistry. Among the wide range oI cytokines, only interIeron y
was highly expressed in active hypertrophic scars on lymphocytes; it was less expressed in the remission phase
and in control samples. The management oI abnormal wound response can be considered appropriate only iI it
aims at the prevention or minimization oI pathological scarring, and the results can be considered satisIactory
only iI the therapy is successIul in speciIic anomalies related to particular lesions and in strict correlation with
the scarring evolution phase. It is thereIore indispensable to adopt a common clinical classiIication as this will
provide better correlation between the clinical and the biological situation and a better interpretation oI the
mechanisms responsible Ior hypertrophic scarring.
Introduction
Pathological scarring still represents a major challenge Ior reconstructive surgeons. This is
due to many Iactors: poor knowledge oI aetiopathogenesis, the lack oI a rational clinical
classiIication, the absence oI a scientiIic basis oI noninvasive therapy, and the limited
results oI treatment.
The importance oI the management oI pathological scars must not however be
underestimated, as they represent one oI the most important limited Iactors Ior the complete
recovery oI patients.
Even today, the diagnosis is based mainly on clinical judgement, since no laboratory test is
yet capable oI evaluating the current state oI a skin scar or oI predicting its evolution,
healing time, and Iinal outcome. Also, owing to the subjective nature oI the evaluation oI
lesions and to the lack oI correlation between clinical status and biological evolution, this
type oI diagnosis is not very reliable.
During its evolution, the scar structure undergoes continuous changes, particularly with
regard to its immunogenetic and histomorphological aspects, and even iI a number oI
histological, immunological, and biochemical studies have provided an abundance oI new
evidence about the diIIerent aspects oI pathological scarring, the real diIIiculty lies in
interrelating all the single elements to each other and to clinical Iindings.
The biological phase oI the scar cannot be evaluated by any standard classiIication criteria,
as it is not correlated to the real evolutive state. This lack oI classiIication makes it
impossible to conduct an accurate investigation oI the various everchanging aspects oI
pathological scarring. Scars have a poorly deIined anatomopathological classiIication, the
epidemiological data are controversial, and the risk Iactors are unknown.
Our experience has led us to believe that the Iirst step towards a correct analysis and
understanding oI this phenomenon is the collection oI epidemiological data, and it is
thereIore necessary to adopt a common clinical classiIication in order to permit, Iirst oI all, a
comparison oI case reports.
On the basis oI these considerations, we elaborated a classiIication chart according to the
morphological aspects oI pathological scars, thus obtaining a better and more homogeneous
patient grouping. This takes into account: hypertrophy, hypertrophy and contracture,
contracture, and atrophy %able 1).
A. Hypertrophy generalized short
intermediate
limited long
B. Hypertrophy and
contracture
generalized short
intermediate
limited long
C. Contracture
D. Atrophy

Table I - linical classiIication oI post-burn pathological scars

Hypertrophy is the most Irequently encountered pathology, either alone or in combination
with other pathologies, especially contracture, at the same time in the same patient. Some
biological aspects oI hypertrophy are well known, such as continuous collagen production,
extracellular matrix abnormalities, in particular chondroitin sulphate distribution,
neovascularity, and increased cell turnover.
linically, the hypertrophic scar is a Iibrous elevated skin lesion that normally does not
exceed the limits oI the original injury, subsiding spontaneously aIter an initial activation
phase Iollowed by a phase oI regression. Initially it is erythematous, elevated, painIul, and
pruritic, suggesting an inIlammatory phenomenon. This phase may persist Ior long periods
oI time and varies considerably Irom individual to individual.
The end oI the activation phase is marked by a progressive decrease oI the inIlammatory
symptoms.
AIter months or even years, the scar Ilattens, soItens, and blanches and there is a reduction
in dysaesthesia. These phases correspond to the various important modiIications in the
tissues, particularly with regard to immunocompetent cell and cytokine production.
In active hypertrophic scars activated T cells represent 70 oI leukocyte inIiltrates,
compared with a maximum oI 30 in normotrophic scars, where inIiltrates are less
abundant Fig. 1). This suggests that immunocompetent cells play a pivotal role in the
mechanisms that lead to hypertrophy.
D3, D4, and D8 T cells diIIer signiIicantly in active hypertrophic scars when compared
with those observed in regressive hypertrophic scars and normotrophic scars (p ~ 0.0001)
Fig. 2). Lymphocytes inIiltrate the deep and superIicial dermis and are also observed in the
epidermis.

ig. I - Percentage oI activated T lymphocytes in
post-burn scar tissues.
ig. 2 - D3, , D8 lymphocytes per 0,25 MM2
in scar tissues.

AIter activation, the T cells release several cytokines, intercellular signals that show major
changes as they pass Irom the active to the regressive phase. With regard to the tumour
necrosis Iactor B (T B), the transIorming growth Iactor 8 (TG B), and interleukin6 (IL-
6) positive samples, there are no signiIicant diIIerences in the active and regressive phase oI
hypertrophic scars or in controls Fig. 3).
The number oI positive specimens Ior interleukin-IB (ILAB) is signiIicantly higher in all
hypertrophic scars than in normotrophic scars, while the percentage oI positive samples Ior
turnout necrosis Iactor a (T (x) is signiIicantly lower in active and regressive
hypertrophic scars than in controls.
InterIeron 7 (Iy) positivity is higher in active hipertrophic scars when compared with the
regressive phase and control Fig. 4).


ig. 3 - TGP, TP, IL-6 detection in scar tissues ig. 4 - I7, Tu., IL- 10 detection in scar tissues

It is evident that there are signiIicant diIIerences between the active and the regressive
phases oI hypertrophic scars, while there are no diIIerences between the regressive phase oI
hypertrophy and normotrophic scars. The only changed cytokine in the regressive phase is
I y - which might well be considered a regression marker - and this correlates well with
the clinical evolution.
The onset time Ior the remission phase and the total duration oI hypertrophy regression are
still controversial. According to the classiIication proposed by Muir in 1990,9 we can
consider three groups oI scars: short-term evolution, when they are active Ior a maximum
period oI six months and then remain static Ior some months, aIter which remission begins
and normally becomes complete in one year aIter healing; long-term evolution, when the
activity continues Ior years and the scar oIten spreads to the surrounding normal skin; and
an intermediate group, when they normalize within two years.
As to distribution, scars can he generalized (when they involve all areas oI spontaneous
healing, graIting surIaces, or donor sites) or localized (when limited to some portions oI
these areas %able I).
In burn patients, the importance oI the anatomical region remains to be clariIied:
hypertrophic scarring in Iact seems to be only partially associated with areas traditionally
considered more liable to hypertrophy than others.
When both hypertrophy and contracture are present, there is not only hypertrophy but also
skin coarctation, with a reduction in the surIace area determined by centripetal Iorces oI
variable strength, tending to evolve into atrophy and/or chronic ulceration and to transIorm
into neoplastic lesions.
On the basis oI this classiIication, 293 patients were analysed: 21 were normotrophic,
34 were hypertrophic, 4 had contractures, 29 were hypertrophic with contractures, and
12 were not yet classiIiable.
These data indicate that some kind oI abnormal wound healing process was present in 67
oI burn patients: thus, even iI pathological scarring is extremely Irequent, it is not an
inevitable sequela.
The data also conIirm our conviction that hypertrophy and contracture should be classiIied
separately iI we are to have a better understanding oI the pathophysiology oI pathological
scarring.
With regard to distribution, 3 1 oI scars were generalized and 69 localized. Regarding
the time oI evolution, the data show that 21.5 were short-term, 32.5 intermediate, and
46.0 long-term evolution scars.
As Ior the question oI treatment, we shall limit our observations to noninvasive
management. There are - and always have been - many therapeutic trends but, to quote
Linares,' "with the same degree oI conIusion and controversy as their morphological and
etiopathogenic descriptions, owing to the Iact that there is not enough scientiIic
demonstration oI their eIIectiveness.
Several therapies have been proposed Ior hypertrophic scars, and this diversity reIlects the
clinical heterogeneity oI such lesions. They can be treated with physical methods, such as
Pressure devices, cryotherapy, and laser therapy, or with pharmacological methods, such as
topical therapy with retinoic acid and intralesional corticosteroid injection, while recent
preliminary reports have suggested that human recombinant interIeron y exerts a successIul
action.
Pressure by means oI elastic garments and silicon gel sheeting or ordinary tapes are a
much~used and very easy method to obtain a thinning eIIect. The mechanism oI this eIIect
is unknown: many hypotheses have been put Iorward but there is no general agreement.
A number oI researchers have claimed varying degrees oI success, oIten only slight, with
cryotherapy and laser therapy, which induce cell disruption. However, the subsequent
reshaping within the tissues has not been Iully investigated. Good cosmetic results and relieI
oI symptoms have been obtained with radiation therapy. There are however in the literature
reports oI neoplasms and radiation eIIects in body structures, even iI recent research has
demonstrated that appropriate dosimetry and shielding can limit these adverse
eIIects.Topical retinoids have been reported to decrease Iibroblast proliIeration and to
reduce collagen synthesis in vitro, but their true action is unclear. o studies have yet been
perIormed in vivo. The intralesional corticosteroid response rate is extremely variable and
dosage and administration times are arbitrary. Also, steroid deposition may lead to
hypopigmentation, atrophy, telangectasis, and/or necrosis. Steroids have been shown to
produce a systemic response and cannot thereIore be used saIely in generalized hypertrophy.
Our experience includes interesting observations oI intralesional human interIeron, which
shows diIIerent behaviours in the various scar evolution phases.
Our studies demonstrate that interIeron y and its receptor are highly expressed in active
hypertrophic scars and start to decrease at the beginning oI the regression phase (ig. 3).
o trials reported in the literature explain the evolutive status and we must consider whether
the promising results are to be imputed to the drug used in the regressive phase, when the
interIeron y rate is low, or to a dose-related eIIect, when the drug is used during the active
phase.
At present we are unable to answer this question, and Iurther studies are needed to establish
interIeron y's eIIicacy and to justiIy its cost compared with that oI other therapies.
It must also be considered that interIeron, like steroids, has systemic eIIects and can be used
only in restricted scars and not in extensive scarring pathologies. In conclusion, it is
essential in our opinion to adopt a common clinical classiIication, as it has been
demonstrated that the morphology oI each scar not only diIIers Irom patient to patient but
also in the same patient, in areas OI the same scar, and in the diIIerent evolutive phases.
The purpose oI the classiIication is to enable the clinician to make an accurate identiIication
oI the kind and stage oI the scar and to predict the clinical course oI abnormal healing.
urrent clinical classiIication criteria are unsatisIactory, as there is no relationship between
the clinical and the biological situation. This gives rise to an excessive variety oI
aetiopathogenic interpretations oI the mechanism responsible Ior hypertrophic scarring.
When every aspect oI the pathogenesis oI hypertrophy is better understood, it will be
possible to have a sound biological basis on which to plan more eIIective prevention and
treatment oI pathological healing, with minimal complications.
The management oI abnormal wound response can be considered appropriate only iI it aims
at the prevention or minimization oI pathological scarring, and the results can be considered
satisIactory only iI the therapy is successIul in speciIic anomalies related to particular
lesions and in strict correlation with the scarring evolution phase. ailing these conditions,
every attempt to Iormulate a rational treatment will be inadequate and even iI there may be
numerous therapeutic proposals, the net result in most cases will be Irustration.

RESUME. La cicatrisation pathologique continue constituer un gros problme pour les chirurgiens
reconstructiIs, qui doivent se Iier une classiIication anatomopathologique trs approximative et des
donnes pidmiologiques controverses. Pour ces raisons notre groupe de recherche a prpar un tableau
de classiIication bas sur les aspects morphologiques des cicatrices pathologiques. La cicatrice
hypertrophique, la squelle des brlures la plus commune dans notre casuistique, est caracterise par la
maniIestation de certaines particularits cliniques typiques suivie, aprs une priode variable d'activation,
par une phase de rmission. Les Iacteurs qui provoquent cette transIormation radicale des cicatrices ne sont
pas bien compris. Rcemment l'hypoths a t Iormule que certains Iacteurs immunologiques puissent
jouer un rle majeur dans la pathogense des cicatrices hypertrophiques. Pour tudier plus en proIondeur ces
aspects pathophysiologiques, nous avons sommes servis de l'immunohistochimie pour tudier les cicatrices
hypertrophiques actives. ous avons examin une large gamine de cytokines, dont seulement l'interIrony est
hautement exprim sur les lymphocytes des cicatrices hypertrophiques actives; il est moins exprim dans la
phase de rmission et dans les tmoins. La gestion du dveloppement anormal des lsions peut tre dIinie
approprie si elle mire la prvention ou la rduction de la cicatrisation pathologique, et les rsultats
peuvent se considrer satisIaisants seulement si la thrapie russit dans le cas de certaines anomalies
spciIiques lies des lsions particulires et en rigoureuse corrlation avec la phase de l'volution de la
cicatrisation. Il est donc essentiel d'adopter une classiIication clinique commune parce qu'elle pourra nous
donner une corrlation meilleure entre la situation clinique et la situation biologique et une interprtation
meilleure des mcanismes responsables de la cicatrisation hypertrophique.

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Acknowledgement. This work was supported by
the Piedmont oundation Ior Burns Study and Research.
This paper was received on 25 ebruary 1997.

Address correspondenee to: Dr Gilberto Magliacani,
Divisione di hirurgia Plastica e entro Ustioni, .T.O.,
Via Zuretti 29, 10126 Torino, Italy (Tel.: 011.6933435;
ax: 011.6933552).

4th Congress of Pan-Arab Association for
urns and
Plastic Surgery (PAPS)
2nd Congress of Syrian Aesthetic
Reconstructive
Surgery and urn Association (SARSA)
14 - 17 September Aleppo-Syria

Topics: ew Trends in Plastic and Aesthetic Surgery, Hand and eck Surgery
Reconstruction oI the Upper and Lower Extremity Burns Management and Prevention
Disaster and Emergency Medicine ongenital deIormities

or inIormation contact: Dr A. Dayoub - President PABPS
Aleppo, Syria
Tel.: 963-21 - 641501/2 - 218044 - 645710
ax: 963-21 - 644900
P.O. Box: 6657