Annals of Burns and Fire Disasters - vol. XII - n. 1 - March 1999

CLASSIFICATION OF PATHOLOGICAL BURN SCARS

Magliacani G., Stella M., Castagnoli C.

Unità Operativa Autonoma di Chirurgia Plastica e Centro Ustioni, Azienda Ospedaliera CTO/CRF/M.
Adelaide, Turin, ltaly

SUMMARY. Tissue repair is a complex phenomenon and various kinds of stimuli may alter the healing process, causing scar anomalies from hypertrophy to chronic ulcers. Owing to the lack of a rigorous clinical classification, a defective knowledge of actiopathogenesis and physiopathological mechanisms, and the difficulty of interpreting research findings, the inclusion of pathological scars in nosological groups remains an unresolved problem. Current diagnostic criteria, based on subjective assessment, do not make it possible to give anything more than an approximate evaluation of the precise evolution phase and clinicians are unable to predict the possible evolution, the timing, and the final outcome. The Authors, on the basis of their research and bibliographic reports, propose a clinical classification, justified by numerous observations that demonstrate the different biological status of scar tissue, providing the biological support on which to base the choice of therapy and the best timing of its initiation.

The process of tissue repair is a complex and dynamic phenomenon that hinges on various biochemical, cellular, and molecular processes in which a considerable number of cells are subjected by a variety of different mediators to a myriad of varying and sometimes contradictory messages, the role of which is not yet fully understood. It is still uncertain how the cells select the appropriate response.
Although substantially similar to the process observed after other kinds of trauma, the repair process in a burn lesion, especially if the burn is extensive, is somewhat different because of the greater hypoxia in the damaged tissue, the considerable amount of oedema, the great quantity of necrotic tissue (capable of causing its own inflammatory reaction with the release of mediators), the progressive secondary damage, and an inflammatory reaction that is retarded but of greater intensity and duration.
As various kinds of stimuli may alter the delicate balance of opposing actions that intervene during the healing process, it is clear that in thermal trauma, because of the characteristics of the damaged tissue and the reactive phenomena secondary to tissue damage, various kinds of scar tissue anomalies are commonly observed, ranging from hypertrophy to chronic ulcers.
However, despite their frequency and gravity, the inclusion of the various forms of pathological scars in nosological groups remains an unresolved problem. This is due to the concurrent existence of a number of negative factors, of which the most important are:'

• lack of a rigorous clinical classification
• defective knowledge of actiopathogenesis and physiopathological mechanisms
• difficulty of interpreting research findings

Current diagnostic criteria are based on subjective assessments and leave an ample margin for personal interpretation of a lesion. They do not make it possible to give anything more than an approximate opinion of the precise moment of its evolution. Thus no clear correlation is established between the clinical situation and the biological situation, a factor of considerable importance for the clinician, who is thus unable to predict the type of possible evolution, the timing, and the final outcome. Also, not uncommonly, the clinician's therapeutic objectives lead only to partial success or recidivation. The lack of organic and comparable technological studies and the difficulty of comparing results of different methods of treatment constitute further evidence of the confusion surrounding this pathology.
The most recent studies, which have provided a considerable amount of information on the various aspects of scar tissue, have underlined two important aspects of the problem:

• the practical difficulty of relating clinical evidence with the biological state of scar tissue, which is characterized during its evolution by a series of continuous modifications;
• the difficulty to assess - thus explaining the different and often conflicting interpretations - research data that are often obtained on samples that are similar but have been classified in different manner.

To this regard, it is a serious shortcoming that there is no clear clinical classification that precisely identifies the type of scar and the moment of its evolution. Such a classification would enable researchers to determine with greater accuracy the changing aspects of pathological scarring.
The first step for an exhaustive analysis that would make it possible to interpret results, facilitate the solution of controversy, and permit a full understanding of the phenomenon must therefore be a collection of comparable epidemiological data that can only be obtained through use of a method of classification that is common to all.
A careful critical clinical observation permits the identification in scars of three different pathological forms that may be present either alone or, not uncommonly, combined with the others, at the same time and in the same patient. In particular, there is a type of association, present in 27.5% of a group of 398 patients we studied,' who presented hypertrophy and retraction simultaneously in the same lesion. This form could represent a separate and distinct pathology and therefore it is not unreasonable to hypothesize the existence of a fourth type in the classification.
In our opinion pathological sears can be distinguished in the following types:

1. Hypertrophie
2. Retracting
3. Atrophic
4. Hypertrophic-retracting

Pure hypertrophy is the most frequent anomaly (about 45% of our cases) and also the most complex. This form has attracted the attention of researchers.
Although many of its biological features are well known it is still not possible to formulate conclusive hypotheses regarding its aetiology and the physiopathological mechanisms underlying it.
Between two and eight weeks after re-epithelialization we observe the onset of aggressively aggravating erythema, pruritus, or pain, while the scar itself gradually assumes the characteristic appearance of a fibrous raised erythematous lesion.
The accumulative presence of these symptoms indicates the activation phase of a hypertrophic scar.
After some months or years the dysaesthesia disappears and the scar becomes lighter in colour, softer, and flatter. This transformation, the duration of which varies from person to person, indicates the passage to the regressive phase.
The process concludes with complete remission, the scar tissue becomes stable, and the scar is clinically mature.
The results of research confirm that the initial symptomatology is accompanied by important modifications in the tissue, which suggest the existence of an inflammatory type of phenomenon in which the immune competent cells take on a central role in the mechanism leading to hypertrophy.
Scar tissue contains a rich cellular infiltrate in which during the activation phase about 70% of the elements are represented by activated T lymphoeytes. These drop in number to little more than 40% in the remission phase and only 36% in stabilized scars, a value similar to that observed in nonnotrophic scars.
Significant differences have been observed between the activation phase and the regression phase in hypertrophic and normotrophic scars also as regards the content of CD4 and CD8 cells, particularly in the region of the subpapillary dermis (Table 1).

An investigation into the state of activation and functional differentiation of T cells infiltrating the hypertrophic scar at clonal level indicated a clear polarization in the direction ThO-Thl, with high production of IFN-), and modest quantities of IL-4 in the active scar, as well as a differentiated picture in scars in the remission phase, also in the direction ThO-Thl but with inverted values and IFN-y levels 4-6 times lower (Table II)

Recent studies of some chemokins has demonstrated, particularly at dermal level, significantly high quantities in hypertrophic scars, particularly of IL-15 and IL-8, with higher values in active scars than in those in the remission phase (Table III).

Research on the inflammatory cytokines produced by the lymphocytes has also evidenced important changes that occur in the passage from the activation phase to the remission phase. The most significant variations are in the TNF-a values, which are lower, and in interleukin-lp values, which are higher with modest or no differences between the active and the remission faces, while INF-y is not only higher in hypertrophy than in controls but also shows differences between the active and the remission phases (Table IV).

In cultures from hypertrophic scars the study of membrane markers has revealed the presence of ectopic markers of fibroblasts and keratinocytes, in particular, with regard to the latter, IFN-gammaR and CD36, confinning the presence of different states of evolution in hypertrophic scar (Table V).

When the remission phase concludes with stabilization of scar tissue, which corresponds clinically to the scar's maturation, all the values observed in the tissue indicate a gradual return to those of normotrophic scars.
The data obtained in these studies confirm the sometimes very significant changes that occur during the scar's evolutionary phase, indicating the existence before final stabilization of at least two clearly distinguished phases that are already well known in the clinical study of hypertrophic scars.
These correspond to two different moments in the transformation of scar tissue with a potentially different evolution characterized by a different balance between opposed activities: proliferation and cellular death, synthesis and degradation of collagen, angiogenesis and vascular remodelling.
This also justifies the need for a more accurate and detailed classification that will enable us to pinpoint the exact moment of the transformation so that it will be possible to achieve a more beneficial therapeutic approach.
In the definition of hypertrophic scars it is therefore indispensable to speak of the active phase, the remission phase, and the stabilization phase. These are different states which it is essential to be able to recognize not only because of their significance for prognosis but also with a view to effective treatment and cure of tissue damage.
As the time necessary for completion of the various phases varies considerably, hypertrophic scars must be subdivided into three groups, in relation to the time necessary for complete remission:

• short-term evolution: these scars remain active for a maximum period of six months followed by stabilization and, after some more months, regression, leading to complete remission, generally within one year;
• medium-term evolution: scars normalize within two years;
• long-term evolution: scars remain active for many years and sometimes involve adjacent skin. According to some researchers this type must be considered a keloid, the extreme form of hypertrophic scar, even if clinical observations are not always able to establish whether it is a true invasion of the surrounding tissue or an intense hypertrophic reaction affc,.ting adjacent tissues that are only slightly & ed.'

Finalil s the extent and anatomical distribution of hypertrophies are extremely variable, it has been thought useful to group them into generalized hypertrophies, when they are ubiquitous and involve all the damaged areas (whether healing spontaneously or with the use of skin grafts and donor sites), and localized hypertrophies, if they are limited to a few zones.
The value of some mediators, particularly Interferony and IL-18 which are identifiable as remission markers because of their behaviour, can provide useful information in clinical diagnosis. Other means of diagnosis are echography and videocapillaroscopy,' which give useful indications as to the evolutionary stage of the scar.
Echography can reveal increases or reductions in the thickness of scar tissue, respectively in the phases of activity and remission. Videocapillaroscopy allows the observation of the great number and the disorder of the vessels in the subpapillary plexus in the activity phase and a gradual, though incomplete, return to normality as the phase of stabilization approaches. Although important for functional purposes, the retracting scar is less frequent (3.7%), is characterized by cutaneous coarctation with reduction of the surface that is provoked by centripetal forces of variable intensity, and is situated typically, but not exclusively, in articular areas. Atrophic scars are rare (0.25%). They have a thin and whitish appearance and an occasional tendency to transfoini into neoplastic lesions. In conclusion, we are convinced that the adoption of a common classification of pathological scarring is a priority if we are to achieve our final therapeutic objective.
By correlating the clinical with the biological state it.
At the same time, clinicians will be able to formulate a more correct diagnosis and express more realistic prognostic assessments of the possible development of scars. They will also dispose of a wider range of useful patology.

RESUME. La réparation des tissus est un phénomène complexe influencé par une large gamme de facteurs qui peuvent causer des anomalies cicatricielles qui vont de l'hypertrophie aux ulcères chroniques. A cause de l'inexistence d'une classification clinique rigoureuse, de la compréhension incomplète de l'étiopathogenèse et des mécanismes physiopathologiques, et de la difficulté d'interpréter les résultats des recherches, il est encore impossible de diviser les cicatrices pathologiques en catégories nosologiques. Les critères actuels diagnostiques sont basés sur des évaluations subjectives de la phase précise de l'evolution de la cicatrice avec le résultat que le clinicien est dans l'impossibilité de prédire l'évolution possible, le temps nécessaire, et le résultat final. Les Auteurs, sur la base de leurs recherches et des relations bibliographiques, proposent une classification clinique justifiée par leurs observations qui définissent les diverses conditions du tissu cicatriciel et fournissent le support biologique sur lequel il est possible de choisir la meilleure thérapie et le moment le plus approprié pour la commencer.

1. Linares H.: Solving the hypertrophic healing problem: are we searching in the right direction? Proceedings of 13th SIU Congress, Magliacam G., Teich Alasia S. (eds), Giuseppe de Nicola, Naples,8 1998.
2. Magliacani G., Stella M., Castagnoli C., Trombotto C., Ondei S., Calcagni M.: Post-burn pathological scar: clinical aspects and therapeutic approach. Ann. Burns and Fire Disasters, 10: 105, 1997.
3. Linares H.A.: From wound to scar. Burns, 22: 339-52, 1996.
4. Stella M.: Esperienza personale nell'epidemiologia delle cicatrici patologiche post-ustione. Proceedings of 13th SIU Congress, Magliacam G., Teich Alasia S. (eds), Giuseppe de Nicola, Naples, 1998.
5. Castagnoli C., Trombotto C., Ondei S., Stella M., Calcagni M., Magliacam G., Teich Alasia S.: Characterization of T-cell subsets infiltrating post-burn hypertrophic scar tissues. Burns, 23: 565-72, 1997.
6. Novelli F., Bemabei P., Rigamonti L., Ariotti S., Stella M., Castagnoli C.: Ruolo funzionale dei linfociti T infiltranti l'epidermide ed il derma delle cicatrici ipertrofiche post-ustione. Proceedings of 13th SIU Congress, Magliacam G., Teich Alasia S.(eds), Giuseppe de Nicola, Naples, 1998.
7. Musso T., Trombotto C., Millesimo M., Ravarino D., Stella M., Teich Alasia S., Magliacani G., Castagnoli C.: 1 fattori chemotattici nelle cicatrici. Proccedings of 13th SIU Congress, Magliacani G., Teich Alasia S. (eds), Giuseppe de Nicola, Napies, 1998.
8. Stella M., Castagnoli C., Trombotto C., Calcagni M., Magliacani G., Teich Alasia S.: Interrelationship between immunocompetent and structural cells in post-burn scars. Fur. J. Plast. Surg., 21: 8-13, 1998.
9. Risso D., Stella M., Calcagni M., Magliacani G., Castagnoli C.: La videocapillaroscopia dinamica a sonda ottica nelle cicatrici ipertrofiche. Studio preliminare. Proceedings of 13th SIU Congress, Magliacani G.,Teich Alasia S. (eds), Giuseppe de Nicola, Naples, 1998.
10. Muir I.F.K.: On the nature of keloid and hypertrophic scars. Brit. J. Plast. Surg., 43: 61-9, 1990.