Hypertrophic scars: causes, symptoms, diagnosis, treatment

Hypertrophic scars are often combined into a group of pathological scars with keloid scars due to the fact that both types are characterized by excessive formation of fibrous tissue and occur as a result of prolonged inflammation, hypoxia, secondary infection, and decreased local immunological reactions. Endocrinopathy is sometimes found in the anamnesis of such patients.

However, unlike keloid scars, hypertrophic scar growth begins immediately after healing and is characterized by the formation of "plus tissue" over an area equal to the wound surface. Subjective sensations are absent. The dynamics of the change in scar color from pink to whitish occurs within the same time frame as normotrophic scars. Prolonged inflammatory reaction, impaired microcirculation and hypoxia, delayed reparative processes contribute to the accumulation of decay products in the wound, causing activation of fibroblasts. their synthetic and proliferative activity.

As a result, excessive collagen accumulation occurs at the site of the skin defect. Collagen formation prevails over its breakdown due to increased synthesis of collagen protein, resulting in fibrosis and scars acquiring a relief that rises above the skin surface. It is known that hypertrophic scars contain fewer fibroblastic cells than keloid scars, and there are no giant, immature forms, "growth zones". It has been proven that collagen synthesis in keloids occurs approximately 8 times more actively than in hypertrophic scars, which explains the lower quantitative content of collagen fibers in hypertrophic scars, and, consequently, the mass of the scar. The qualitative composition of collagen also has differences. Thus, in young hypertrophic scars, an increase in collagen types I and III, as well as an increase in dimer (beta chains) was found.

Comparative clinical characteristics of keloid and hypertrophic scars

Type of scars	Keloid scars	Hypertrophic scars
Clinical picture	Bluish-red color, (+ tissue). Increase in all directions, itching, paresthesia. The decrease in the brightness of the color and volume of the scar occurs very slowly, over several years. Sometimes the scar does not change at all with age.	Raised above the skin level - (+ tissue). Subjective sensations are absent. The color changes, in terms of time as with normal scars.
Dates of appearance	After 2-3 weeks, sometimes after several months and years after the injury.	Immediately after wound epithelialization.
Reason for appearance	Genetic and ethnic predisposition, endocrinopathies, immunological shifts, impaired adaptive capacity of the body, chronic stress, secondary infection. Chronic inflammation, hypoxia, impaired microcirculation.	Decreased local reactivity, secondary infection, disruption of microcirculation, and as a consequence - chronic inflammation, hypoxia. Endocrinopathy is possible.

Structure of keloid and hypertrophic scars

Histological picture of a growing keloid

The epidermis is thinned, consists of 3-4 layers of cells, among which cells of a shape atypical for different layers of the epidermis predominate. There is vacuolar dystrophy of keratinocytes, smoothing of the papillary pattern, hypoplasia of the spinous layer, weak perifocal vacuolization of individual spinous cells, an increase in melanin-containing basal cells, karyopyknosis. The stratum corneum is unchanged or thinned. An increase in the number of melanin granules in melanocytes and basal keratinocytes is noted.

Keloid scars are divided into three zones: subepidermal, growth zone, and deep zone.

In the upper, subepidermal sections there is - smoothing of the epidermal processes and dermal papillae, phenomena of non-specific inflammation, mucoid swelling of collagen fibers. In the subepidermal layer - foci of young connective tissue with the so-called "growth zones" located at a depth of approximately 0.3-0.5 cm. The growth zone consists of foci represented by a concentric accumulation of fibroblasts, in the center of which there is a segment of a regressing capillary. It is believed that the capillary pericyte is a stem cell for fibroblasts. Therefore, clusters of cells in the growth zones are pericytes transforming into fibroblasts. Collagen fibers in the growth zones are in the form of loose unoriented bundles with immature collagen fibrils, 250-450 A (angstroms) in diameter, in the stage of mucoid swelling. Some "stretching" and chaotic orientation are noted due to increased tissue turgor due to edema. Along with thick ones, thin "communication fibers" are also found. Keloid scars contain a large number of functionally active, poorly differentiated, young and pathological (giant) fibroblasts, ranging in size from 10x45 to 12x65 μm. with increased metabolism (70-120 in the field of view). Many authors note a reduced number of vessels in keloid scars compared to physiological and hypertrophic ones. This may be a relative decrease in the total area of the vascular bed in relation to the area of scar tissue. However, it is obvious that there are significantly more vessels in growing keloid scars than in old ones.

In the middle sections of the scar, a variegated morphological picture is observed. caused by a combination of extensive tissue regions with thick, randomly oriented collagen fibers, with foci of young connective tissue localized in the thickness of the scar and loci of dystrophic changes and inflammatory reactions. The main structural protein of the keloid is collagen. Collagen bundles are characterized by loose packing and disorientation. The thickness of collagen fibers is from 8 to 50 μm. The most massive collagen fiber bundles are in the middle zone of the keloid. Between the collagen fibers, there are various populations of fibroblasts - from immature and giant to fibrocytes with a typical elongated shape and normal size. There is hyaline deposition in the middle and upper parts of the dermis. Rare focal lymphocytic-histiocytic infiltrates around the vessels of the superficial and deep network. There is a small number of elastic fibers and vessels (1-3 capillaries in 1-3 fields of view at x504 magnification).

In the interstitial substance there is edema, hyaluronic acid and sulfated fractions of glycosaminoglycans predominate, which is considered one of the signs of an immature state of connective tissue.

In the middle and deep layers of the scar, the number of cellular elements and interstitial substance is reduced. An increase in the number of morphologically mature forms of collagen fibrils is noted. The most massive collagen bundles are in the middle zone of the keloid. With increasing age of the scar, fibrosis and sclerosis of collagen of the lower part of the dermis and hypodermis are noted.

Vessels: There are two types of capillaries in a keloid scar - distributive and functional. In the distributive ones - stasis, congestion, which causes the cyanosis of keloid scars. Diapedesis of erythrocytes is noted, which indicates tissue hypoxia. In the subepidermal layer of vessels - 3-5 in the field of vision, in the growth zones - 1 vessel per 1-3 fields of vision. Functional or feeding capillaries have a lumen of no more than 10 microns, some are in a reduced state.

The cellular population of keloids is represented by rare lymphocytic-histiocytic infiltrates around the vessels and an abundance of fibroblastic cells. Fibroblasts - 38-78 cells in the field of view at magnification x 504. Atypical giant fibroblasts are a pathognomonic sign of keloid. Young fibroblasts make up the overwhelming majority of the population. Attention is drawn to the tendency of young cells to symplastogenesis and the formation of growth foci, which are foci of immature connective tissue localized perivascularly. Outside the growth foci, fibroblasts lie among collagen fibers.

The absence of plasma cells and a small number of lymphoid cells at various stages of keloid scar formation are typical signs.

The pyroninophilic cytoplasm of fibroblasts indicates their high biosynthetic activity. Fibrocytes are found in the middle and deep layers of the scar, the presence of which reflects the progress of the tissue maturation process.

There are also mast cells and polyblasts.

Epidermal derivatives (sebaceous, sweat glands, hair follicles) are absent in keloid scars.

The division of keloid scars into young (up to 5 years of existence) and old (after 5 years) is quite arbitrary, since we observed active keloids at the age of 6-10 years. However, the process of aging (maturation) of keloid scars also occurs and is stabilized, and the "old" keloid scar changes its clinical and morphological picture. The morphological picture of keloid scars of different ages is presented in the table.

Morphology of keloid scars

Age of the scar	Growing keloid (young - up to 5 years)	Old keloid (after 5 years)
Subepidermal layer	Thin epidermis, smoothed papillae. Macrophages, young, atypical giant fibroblasts, thin bundles of collagen fibers. Vessels 3-4 in the field of vision	Epdermis with smoothed papillae. Pigment cells with lipofuscin grains accumulate. Collagen fibers are arranged in bundles parallel to the epidermis, with a small number of fibroblasts, vascular macrophages, between them.
The "growth zone" is represented by growth foci and loose, immature bundles of collagen fibers.	5-10 times wider. "Growth foci" consist of fibroblast groups and are surrounded by a layer of reticulin and collagen fibers. There are 1-3 vessels in 1-3 fields of vision. The intercellular substance is mainly represented by hyaluronic acid and glycosaminoglycan fractions. There are no plasmatic, lymphoid cells, few mast cells.	There are 3-5 vessels in the field of vision, the number of fibroblasts decreases. Collagen fibers become denser, the amount of acidic mucopolysaccharides decreases. Plasma and lymphoid cells appear, the number of mast cells increases.

Histological picture of a young hypertrophic scar

The epidermis, depending on the shape and size of the scar, can be thickened or normal. The border between the epidermis and the upper part of the scar is often a sharply expressed acanthosis. However, it can be smoothed, without pronounced papillae.

Comparative histological characteristics of keloid and hypertrophic scars (according to literature data)

Histological picture	Keloid scars	Hypertrophic scars
"Growth Spots"	There is a large amount in the middle layer of the scar.	Absent.
Epidermis	Thinning, smoothing of epidermal papillae	All layers are thickened, acanthosis, often mitosis in the spinous layer.
Cellular elements	There are no lymphocytes, plasma cells, few mast cells, and groups of polyblasts.	Extensive lymphoplasmacytic perivascular infiltration.
Fibroblasts	78-120 in sight, many varieties represented.	57-70 in sight.
Giant fibroblasts	Many, ranging in size from 10x45 to 12x65 microns.	None.
Myofibroblasts	None	Prevail
Collagen fibers	Thickness from 250 to 450 A in the upper layer, deeper - from 50 µm in the form of loose, unoriented bundles with mucoid swelling, surrounding the foci of growth.	From 12 to 120 microns. Collected in bundles, lie wavy and parallel to the scar surface.
Glycosaminoglycans	In large quantities, hyaluronic acid predominates, sulfated fractions of glycosaminoglycans	In moderate quantities, chondrontin sulfates predominate
Elastic fibers	It is present only in the deep layers of the scar.	They are located parallel to the bundles of collagen fibers
Epidermal derivatives (hair follicles, sebaceous, sweat glands)	None.	The number is slightly reduced compared to normal scars.
Vessels	1-3 in 1-3 fields of vision in the “growth zone”, in the subepidermal layer 3-4 in 1 field of vision.	2-4 in 1 field of view.

In the upper, subepidermal sections of young hypertrophic scars, smoothing of the epidermal processes and dermal papillae is noted. Loosely arranged thin collagen fibers in the intercellular substance, vessels, cellular elements (lymphocytes, mast cells, plasma cells, macrophages, fibroblasts). There are more fibroblasts than in normal scars, but approximately 1.5 times less than in keloid scars. Collagen fibers in the upper sections are thin, have a loose orientation and are located in the intercellular substance, where chondroitin sulfates predominate. In the lower sections, they are collected in bundles, oriented horizontally, their diameter is thicker. In the lower sections of the scar, the density of bundles is higher, and there is less intercellular substance. There is an insignificant amount of elastic fibers.

In the middle sections of the scar, the scar tissue consists of horizontally oriented collagen fibers, vessels, interstitial substance and cellular elements, the number of which is reduced compared to the upper sections of the scar.

Depending on the age of the scar, the ratio between cellular elements, vessels, interstitial substance and the mass of collagen fibers changes towards the predominance of fibrous structures, namely collagen fibers.

There are 2-3 times more fibroblastic cells in hypertrophic scars than in a normal scar (57-70 per field of vision), there are no giant, immature forms. Normally, there are 15-20 fibroblasts per field of vision. Some authors note the presence of large, branched fibroblasts rich in actinic filaments in hypertrophic scars, which are called myofibroblasts. It is believed that due to these actinic filaments, fibroblasts have a high contractility. It was also suggested that the connection of actinic filaments of myofibroblasts with extracellular fibronectin located on collagen fibers limits the growth of hypertrophic scars. Some consider this theory far-fetched, since fibroblasts are actively moving cells due to their ability to form long processes. Actinic filaments, in all likelihood, are the contractile apparatus that helps cells move. Moreover, in electron microscopic studies we found them in fibroblasts of keloid scars and in normal fibroblasts of the dermis.

Vessels: In the subepidermal layer of the hypertrophic scar there are 3-5 vessels per field of vision.

In the middle sections - 2-4 in the field of vision.

Epidermal derivatives. In hypertrophic scars, along with deformed ones, there are normal hair follicles, sweat and sebaceous glands, but in smaller quantities than in ordinary scars.

Elastic fibers: located parallel to the collagen fiber bundles.

Glycosaminoglycans: chondroitin sulfates predominate.

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