Pathogenetic features of hypertrophic scars

Kristina Novak (Mushikhina) , otorhinolaryngologist, plastic surgeon, specialist in contour plastic surgery, graduate student of the Department of Otorhinolaryngology of NMU named after. O.O. Bogomolets

A hypertrophic scar is a scar that is a relatively mature connective tissue protruding above the level of the surrounding skin (4-5 mm), which is covered with a thin layer of epidermis.

Morphohistological features

Peeling and trophic ulcers may be present on the surface of the scar.

The histology of a hypertrophic scar appears as a structure rich in specific fibrocytes (similar to the pattern of keloids), which are several concentric and organized parallel to the surface of the skin.

A hypertrophic scar can form on any part of the body after various types of trauma to the skin surfaces. It can often occur after surgical correction of a normotrophic scar as a consequence of a complication.

Pathogenetic mechanism of development of hypertrophic scars

Many studies have been conducted to identify the origin of hypertrophic scars.

Research shows that 26-40% of hypertrophic scars are associated with symptoms such as itching, unpleasant tingling, and pain.

When the connective tissue reacts excessively to injury against the background of unfavorable healing conditions (inflammation, scar stretching, etc.), hypertrophic scars are formed. Under conditions of hypoxia and inflammation, fibroblasts are activated by biologically active substances, and undifferentiated, pathological, functionally active cells with a high level of collagen synthesis appear. The formation of collagen prevails over its breakdown due to a decrease in the production of collagenase, a specific enzyme that destroys collagen, as a result of which powerful tissue fibrosis develops in the form of hypertrophic or keloid scars. Hypertrophic scars are often combined into a group with keloid scars due to the fact that both types are characterized by excessive formation of fibrous tissue and arise as a result of inadequate inflammation, the addition of a secondary infection, a decrease in local immunological reactions, etc.

Differential diagnosis with keloids

A keloid has a different macroscopic structure from a hypertrophied scar, and this difference is demonstrated by its histological appearance. The key difference is that keloids are invasive to surrounding tissue and are extruded from the edges of the wound. The consistency of a keloid and a hypertrophic scar can sometimes be similar, although vertical growth of a keloid is often more common than hypertrophic scars.

Key differences between kelod and hypertrophic scars [1]

Visual clinical and histological [2] picture of hypertrophic scars

Visual clinical and histological [2] picture of keloid scars

Factors influencing the formation of hypertrophic scar

Factors are divided into general and local.

Local factors: localization of the wound, nature and extent of damage, quality of wound drainage.

General factors: age, immune status, heredity. It is practically important that during the third stage of scar formation, external forces influence.

If in patients the processes of fibrillogenesis are initially enhanced and prevail over the processes of collagenolysis, hypertrophic scars will most likely form, and in the worst case, keloids. This increase in the production of fibroblasts (also called myofibroblasts) can also over-activate their ability to synthesize extracellular matrix, so fibroblasts are both more numerous and more productive. An overactive inflammatory mechanism increases pH and therefore increases the risk of hypertrophic scar formation.

All of the above factors contribute to the formation of a hypertrophic scar, histologically appearing as fibrous tissue with collagen fibers that are randomly connected into loose sheets and randomly oriented on the surface of the epithelium. Myofibroblasts, which replace fibroblasts in the keloid scar, differ in their cytoplasmic microfilament bundles with nuclear indentations and intercellular connections.

Working classification

Hypertrophic scars are formed in cases where collagenolysis predominates, and as a result, the tissue response to trauma intensifies. In connection with this response of the body to trauma, three degrees of amplification are distinguished: weak, moderate, significant, and based on this, hypertrophic scars of types I, II and III are divided (classification by A.E. Belousov [3])

Hypertrophic scars type I

They are characterized by weak clinical symptoms (protrude slightly above the skin level, have a dull color, unpleasant subjective sensations are weak, often absent). Symptoms of hypertrophy are expressed in the first 2-3 months after injury (surgery) and gradually weaken. Hypertrophic scars of type I are usually single and are formed in unfavorable local conditions (discrepancy between the axis of the scar and Langer's lines, significant stretching of the tissue acting along the axis of the scar). Hypertrophy of part of the scar is possible. A distinctive feature is the transformation into normotrophic scars when local conditions change to more favorable ones. In this case, additional conservative treatment is usually not necessary.

Hypertrophic scars type II

They are characterized by more pronounced symptoms, larger sizes of the outer part of the scar and its brighter color. Unpleasant subjective sensations associated with the scar are quite pronounced and are one of the main complaints of patients. The intensity of these sensations (along with other symptoms) decreases slowly and only to a certain level. Type II hypertrophic scars can be either single or multiple and can form under relatively favorable conditions. If the patient has extensive hypertrophic scars, some areas of them may be less pronounced or even normotrophic (a similar process is observed when the local conditions of scar formation change, for example, under the influence of surgery). However, the scar retains signs of hypertrophy, which over time can either weaken or intensify under the influence of load. Additional conservative treatment of type II hypertrophic scars provides a noticeable improvement in the outcome.

Hypertrophic scars type III

They are formed under any local conditions and in any anatomical zone. If a patient has multiple scars, all or almost all scars are hypertrophic. The severity of symptoms is significant, and their intensity changes little with increasing age of the scar. Improving the local conditions of scar formation under the influence of surgery can lead to an improvement in its characteristics, however, without additional conservative treatment, this improvement can only be temporary, and the final degree of scar hypertrophy may even increase. On the other hand, conservative treatment in itself can reduce the severity of symptoms, but must be early and long-term.

If only a scar (part) undergoes hypertrophy, experiencing predominantly longitudinal stretching, then the patient experiences a relatively small (weak) increase in the tissue response to injury, and then this is already a type I hypertrophic scar. If any scar undergoes hypertrophy, and not only with longitudinal, but also transverse stretching, there is a significant increase in the general reaction of the patient’s tissues to injury and type III scar occurs. Between these two extremes there are numerous options (type II scar and transitional forms).

Knowledge of this classification gives the doctor the opportunity to assess the type of scar and make a decision on further treatment, which we will talk about in future publications.

Bibliography:

1. Finnson, K. W., McLean, S., di Guglielmo, G. M., & Philip, A. (2013). Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring. Advances in Wound Care, 2(5), 195–214. https://doi.org/10.1089/wound.2013.0429
2. https://emedicine.medscape.com/article/876214-overview#a2
3. "Types of hypertrophic scars and the goals of their correction", Belousov A.E.
4. Insights into the Pathophysiology of Hypertrophic Scars and Keloids: How Do They Differ?/ FM Ghazawi et al. Adv Skin Wound Care. 2018. Vol. 31, no. 1. R. 582-595. doi: 10.1097/01.ASW.0000527576.27489.0f.
5. Recent advances in hypertrophic scar/ J. Zhang et al. Histol Histopathol. 2018. Vol. 33, no. 1. R. 27-39. doi: 10.14670/HH-11-908.