So what is a keloid scar?

I am not sure if the word embarrassing is quite right but we are all, to a greater or lesser extent, part of a scientific community which can send rockets deep into space on the one hand, map the human genome on the other and yet cannot answer the simple question: What is a keloid scar? Of course we all have our individual concepts of what a keloid scar might be, but concepts are one thing, and a well-defined, characterized and categorized entity is another. Part of the problem is that for too many years the term keloid and hypertrophic have been used without clarity and distinction, and this practice continues. A meta analysis of treatments that looks at both keloids and hypertrophic scars is bound to be inconclusive.1 A systematic review of the thoroughness of the Cochrane Style which fails to distinguish between the two types of scar is again going to provide no useful evidence.2 The excellent and comprehensive review which leads this issue of the journal focuses just on keloid disease. Durani and Bayat are reporting on the levels of evidence provided by clinical studies of treatments for keloid scar.3 Their conclusions are as important as they are humbling. There is no good evidence about treatment. Collectively we are failing our patients by not thinking more clearly about what we are dealing with before embarking on clinical studies. Two years ago a review of reviews was published which focused on the differences between hypertrophic and keloid scars.4 I wrote this with my colleague Professor Lin Huang and we concluded that much of the scientific and clinical research in the field of keloid scarring is fundamentally flawed because investigators are failing to define their subject matter. A rather damming comment but it has evoked no dissent. Durani and Bayat succinctly précised this paper and I quote,

`In a comprehensive review of basic science research studies evaluating keloid and hypertrophic scarring, the significant immunohistochemical and morphologic differences between the two scar entities and the significant heterogeneity within each scar type, during different stages of the scar's evolution, were highlighted. The use of the terms ‘hypertrophic response’ and ‘keloid diathesis or disposition’ was recommended, and the authors suggested that studies should be based on accurate molecular characterization of the scar type related to the clinical history and subsequent response to treatment. The variable response to treatment reflects the heterogeneity within keloid scars and future studies may have to first identify cohorts of scar according to molecular profiles, before assessing response to different therapeutic interventions and arriving at conclusions on efficacy. These important concepts have not been adequately addressed in the clinical studies to date.'

The publishers of the journal Plastic and Reconstructive Surgery have kindly given me the permission to reprint a diagram we used in that paper (Fig. 1). This underlines two key differences between keloid and hypertrophic scar, one being the ‘time-line’ and the other being the association with contraction. This latter point is rather interesting and one illustrated by considering a scar on the back of a hand, before and after excision, and a scar on the chin, before and after excision (Figure 2, Figure 3). Both the hand and the face belong to the same patient, and the causative event was the same, a burn. Much can be learnt from the study of such cases but looking at interventions in scars from different causative agents with varying history and a variety of prior treatments leads to confusion not clarity. Another aspect of keloid disease is a variation in severity as is illustrated in Fig. 4. In both patients the initiating event was the same, ear piercing, but the results are remarkably different. Meanwhile new approaches to the keloid scar continue to be explored and a particular research interest of ours is to focus on the control of repair. A few years ago we published a single case report describing the use of cultured keratinocytes on a post-burn keloid scar.5 Our hypothesis was that stem cells within the autologous cell culture, sprayed onto the excisional defect after partial removal of the keloid, were influencing the dermal fibroblasts in matrix deposition and remodeling so that a more ‘normal’ scar resulted. We have now treated several such children and Fig. 5a illustrates a classic keloid scar appearance in the upper anterior helical rim of the right ear, whilst 3 years later, Fig. 5c, the keloid has gone. I have not used this yet on the bridging pre-sternal keloid. I think these may be a rather different type of scar and I wonder if there may be an element of chimerism: a central span with keloid features with some hypertrophic ‘footings’ on either side. Keloid scars remain a fascinating biological phenomenon and we can give a rather long description: a keloid is an abnormal form of scarring (a fibro proliferative disorder) that is characterized by a natural history that is not associated with maturation and regression and by a clinical character that is not associated with contraction. A keloid scar is heterogeneous in nature with more cellular activity at the periphery than in the centre, but with central cells which demonstrate a decreased tendancy to undergo apoptosis. The extracellular matrix and vascular architecture of keloid scars varies within each scar and between scars and is more distinctly different in the spectrum of heterogenicity from that of hypertrophic scarring.

View Large Image Download to PowerPoint

Figure 1 Normal and hypertrophic scars are similar in terms of their ‘cycle’ of matrix proliferation, stabilization, and maturation. Keloid scars rarely ‘mature,’ but there are gross morphologic differences between mild and severe keloids. A diagrammatic representation of hypertrophic and keloid scars demonstrates one essential clinical difference - contraction. Diagram reproduced with permission.4

View Large Image Download to PowerPoint

Figure 2 A hypertrophic scar before (a) and after (b) excision. Note contraction deformity (hyper extension) of little finger MCPJ corrected by excision.

View Large Image Download to PowerPoint

Figure 3 A keloid scar before (a) and after (b) excision. Note no deformity of mouth before or after excision.

View Large Image Download to PowerPoint

Figure 4 a) Mild keloids caused by repeated ear piercing in a Chinese boy. b) A massive keloid caused by ear piercing in an African girl (provided courtesy of Dr Richard Nnabuko).

View Large Image Download to PowerPoint

Figure 5 a) Post burn ear showing classical keloid but also post-auricular hypertrophic scar. b) The keloid was shaved and cell spray applied. The blue colour is gentian violet applied 3 weeks post-cell spray. c) Three year follow up after keloid removal. All scars mature and no recurrence of keloid.

A new conversation stopper in Plastic Surgical circles is to ask the question: What unique biological phenomenon separates humans from animals? After a suitable period of reflective silence throw in the suggestion, keloid scarring? So far I have had only one comeback, and that was from a particularly bright senior resident who ventured, ‘What about nose bleeds?’ I should add that he did his doctoral thesis research on the vascularity of the human nasal septum. But there is another question that gives pause for thought. This was very nicely expressed by Mr Tom Potoker, a renowned burns surgeon from Wales, UK. At a recent meeting of the European Club for Paediatric Burns held in Graz, Austria, Tom asked, what was the possible evolutionary advantage for humans to develop keloid scarring? No answers were forthcoming.

To conclude, as Durani and Bayat have not given a picture of a keloid to put on the front cover we continue with the facial theme. The picture is Fig. 6 from Hontanilla and Auba's study reporting a new 3D capture system for analyzing facial movement, a particularly useful tool for assessing the outcome of facial reanimation surgery.6