Hypertrophic scars: causes, symptoms, diagnosis, treatment

Hypertrophic scars often combine a group of pathological scars in common with keloid scars in connection with that. That both species are characterized by excessive formation of fibrous tissue and arise as a result of prolonged inflammation, hypoxia, attachment of secondary infection, reduction of local immunological reactions. In a history of such patients, endocrinopathies are sometimes found.

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

As a result, excessive accumulation of collagen takes place at the site of the skin defect. The formation of collagen predominates over its disintegration due to an increase in the synthesis of collagen protein, as a result of which fibrosis develops and scars acquire a relief that rises above the surface of the skin. It is known that in hypertrophic scars cells of the fibroblastic series are smaller than in keloid scars, there are no giant, immature forms, "growth zones". It has been proved that the synthesis of collagen in keloids occurs about 8 times more actively than in hypertrophic scars, which explains the smaller quantitative content of collagen fibers in hypertrophic scars, and, consequently, the mass of the scar. The qualitative composition of collagen also has differences. So in young hypertrophic scars, an increase in type I and III collagen was found, as well as an increase in the dimer (beta chains).

Comparative clinical characteristics of keloid and hypertrophic scars

Type of scars	Keloid scars	Hypertrophic scars
Clinical picture	Cyanotic red color, (+ cloth). Increase in all directions, itching, paresthesia. Reducing the brightness of the color and volume of the rumen is very slow, for several years. Sometimes the scar does not change with age.	They rise above the level of the skin - (+ cloth). Subjective sensations are absent. The color changes, in terms of the normal scars.
Date of occurrence	After 2-3 weeks, sometimes several months and years after the injury.	Immediately after epithelization of the wound.
Reason for appearance	Genetic and ethnic predisposition, zondocrinopathies, immunological changes, disruption of adaptive abilities of the organism, chronic stress, attachment of secondary infection. Chronic inflammation, hypoxia, impaired microcirculation.	Reduction of local reactivity, attachment of secondary infection, violation of micro-circulation, and as a consequence - chronic inflammation, hypoxia. Endocrinopathies are 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 the cells of the atypical for different layers of the epidermis form predominate. There is vacuolar dystrophy of keratinocytes, smoothing of papillary pattern, hypoplasia of thorny layer is noted, weak perifocal vacuolization of individual prickly cells, increase in melanin-containing basal cells, karyopicnosis. The stratum corneum is unchanged or thinned. There is an increase in the number of melanin granules in melanocytes and basal keratinocytes.

In the keloid scars, three zones are distinguished: the subepidermal zone, the growth zone, the deep zone.

In the upper, subepidermilitary departments there is a smoothing of epidermal processes and dermal papillae, phenomena of nonspecific inflammation, mucoid swelling of collagen fibers. In the subepidermal layer - the foci of the young connective tissue with the so-called "growth zones" located approximately at a depth of 0.3-0.5 cm. The growth zone consists of foci represented by a concentric cluster of fibroblasts with a regressing capillary in the center. It is believed that the pericyte of capillaries is a stem cell for fibroblasts. Therefore, cell clusters in growth zones are pericytes transformed into fibroblasts. Collagen fibers in growth zones in the form of loose undirected beams with immature collagen fibrils, 250-450 A in diameter (angstroms) in the stage of mucoid swelling. There is some "stretching" and randomness of orientation in connection with the increase of the turgor of the tissue due to edema. Along with thick, there are also thin "communication fibers". In keloid scars, a large number of functionally active, slightly differentiated, young and pathological (giant) fibroblasts, ranging in size from 10x45 to 12x65 microns. With increased metabolism (70-120 in the field of vision). Many authors note a reduced number of vessels in keloid scars compared with physiological and hypertrophic. Perhaps this is 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 the growing keloid scars of the vessels than in the old ones.

In the middle parts of the rumen a mottled morphological picture is noted. Caused by a combination of extensive tissue regions with thick, chaotically oriented collagen fibers, with foci of juvenile connective tissue localized in the cicatrix and loci of dystrophic changes and inflammatory reactions. The main structural protein of the keloid is collagen. Bunches of collagen differ loose packing, disorientation. The thickness of collagen fibers is from 8 to 50 μm. The most massive bundles of collagen fibers are in the middle zone of the keloid. Between the collagen fibers are various populations of fibroblasts - from immature and giant to fibroblasts with a typical elongated shape and normal size. There is a deposit of hyaline in the middle and upper parts of the dermis. Rare focal lymphocytic-histiocytic infiltrates around the vessels of the surface and deep network. There is an insignificant amount of elastic fibers, vessels (1-3 capillaries in 1-3 fields of vision with an increase of x504).

In the interstitial substance, edema, hyaluronic acid and sulphated fractions of glycosaminoglycans predominate, which is regarded as one of the signs of the immature condition of the connective tissue.

In the middle and deep layers of the rumen, the number of cellular elements, interstitial substance is reduced. There is an increase in the number of morphologically mature forms of collagen fibrils. The most massive bundles of collagen in the middle of the keloid. With the increase in the age of the scar, the appearance of fibrosis and sclerosis of the collagen of the lower dermis and hypodermis.

Vessels: Capillaries in a keloid scar of two types - distributive and functional. In distributive - stasis, stagnation, which causes cyanosis keloid scars. Diapedesis of erythrocytes is noted, which indicates the hypoxia of tissues. In the subepidermal layer of the vessels - 3-5 in the field of vision, in the growth zones - 1 vessel per 1 -3 field of view. Functional or feeding capillaries have a clearance 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 the abundance of cells of the fibroblastic series. Fibroblasts - 38-78 cells in the field of view with an increase of x 504. Pathognomonic sign of the keloid are atypical giant fibroblasts. Young fibroblasts constitute the vast majority of the population. Attention is attracted to the tendency of young cells to create and form growth centers, which are the centers of immature connective tissue localized perivascularly. Outside the growth foci, fibroblasts lie among the collagen fibers.

Absence of plasma cells, a small number of lymphoid cells at various stages of keloid scar formation is typical for him.

Pyroninophilic cytoplasm of fibroblasts testifies to their high biosynthetic activity. Fibrocytes occur in the middle and deep layers of the rumen, the presence of which reflects the course of the maturation process of the tissue.

There are also mast cells, polyblasts.

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

The division of keloid scars into young (up to 5 years of existence) and old (after 5 years) is very conditional, as we observed active keloids at 6-10 years of age. Nevertheless, the process of aging (maturation) of keloid scars also occurs and is stabilized, and the "old" keloid scar modifies its clinical and morphological pattern. Morphological pattern of keloid scars of different ages is presented on the table.

Morphology of keloid scars

Age of rumen	The growing keloid (young - up to 5 years)	Old keloid (after 5 years)
Subepidermal layer	Thin epidermis, smoothness of papillae. Macrophages, young, atypical giant fibroblasts, thin bundles of collagen fibers. Vessels 3-4 in the field of view	An epidermis with a smooth papillae. Pigment cells with lipofuscin seeds accumulate. Collagen fibers are bundled in parallel epidermis bundles, between them an insignificant amount of fibroblasts of macrophage vessels.
"Growth Zone" is represented by growth sites and loose, immature bundles of collagen fibers	5-10 times wider. "Growth centers" consist of groups of fibroblasts and are surrounded by a layer of reticulin and collagen fibers. Vessels 1-3 in 1-3 fields of vision. The intercellular substance is represented mainly by hyaluronic acid and fractions of glycosaminoglycans. There are no plasma, lymphoid cells, few obese.	Vessels 3-5 in the field of view, the number of fibroblasts decreases. Collagen fibers are compacted, the amount of acidic mucopolysaccharides decreases. There are plasma, lymphoid cells, the number of obese is increasing.

Histological picture of young hypertrophic scar

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 pronounced acanthosis. However, it can be flattened, without pronounced papillae.

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

Histological picture	Keloid scars	Hypertrophic scars
"Foci of growth"	In the middle layer of the rumen a large number.	Absent.
Epidermis	Thinened, smoothed epidermal papillae	Thickened all layers, acanthosis, in the spiny layer often mitosis.
Cellular elements	There are no lymphocytes, plasma cells, few mast cells, a group of polyblasts.	Extensive lymphoplasmocytic perivascular infiltration.
Fibroblasts	78-120 in the field of view, there are many varieties.	57-70 in sight.
Giant fibroblasts	A lot, the size of 10x45 to 12x65 microns.	None.
Myofibroblasts	No	Prevail
Collagen fibers	Thickness from 250 to 450 A in the upper layer, deeper - from 50 microns in the form of loose with mucoid swelling undirected beams, surround growth centers.	From 12 to 120 microns. They are collected in bundles, lie undulating and parallel to the surface of the rumen.
Glycosaminoglycans	In a large amount, hyaluronic acid predominates, sulfated fractions of glycosaminoglycans	In a moderate amount, chondrontine sulfates predominate
Elastic fibers	There are only deep layers of the scar.	Are located parallel to bundles of collagen fibers
Epidermal derivatives (hair follicles, sebaceous, sweat glands)	None.	The amount is somewhat 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 the 1 field of view.	2-4 in 1 field of view.

In the upper, subepidermal sections of young hypertrophic scars, epidermal processes and dermal papillae are smoothed. Loose thin collagen fibers in the intercellular substance, vessels, cellular elements (lymphocytes, mast cells, plasma cells, macrophages, fibroblasts). There are more fibroblasts than normal scars, but approximately 1.5 times less than in keloids. Collagen fibers in the upper sections are thin, have loose orientation and are in the intercellular substance, where chondroitin sulfates predominate. In the lower parts they are bundled, oriented in a horizontal direction, their diameter is thicker. In the lower parts of the rumen, the density of the bundles is higher, and the intercellular substance is smaller. There is a small amount of elastic fibers.

In the middle parts of the scar, scar tissue consists of horizontally oriented collagen fibers, vessels, interstitial substance and cellular elements, the amount of which is reduced in comparison with the upper sections of the scar.

Depending on the age of the rumen, the ratio between the cellular elements, blood vessels, interstitial material and the mass of collagen fibers changes toward the predominance of fibrous structures, namely, collagen fibers.

Cells of the fibroblastic series in hypertrophic scars are 2-3 times larger than in normal scar, (57-70 in the field of vision), there are no giant, immature forms. Normally, 15-20 fibroblasts are in sight. Some authors note the presence in the hypertrophic scars of large, otroschatyh, rich in actinic filaments, fibroblasts, which are called myofibroblasts. It is believed that due to these actinic filaments, fibroblasts have a great contractile ability. It has also been suggested that the association of actinic filaments of myofibroblasts with extracellular fibronectin located on collagen fibers limits the growth of hypertrophic scars. Some consider this theory to be far-fetched, since fibroblast is an actively moving cell, thanks to the ability to form long processes. Actinic filaments, in all likelihood, are the contractile apparatus that helps cells move. Moreover, with electron microscopy, we detected them in fibroblasts of keloid scars and in normal fibroblasts of the dermis.

Vessels: In the subepidermal layer of the hypertrophic rumen of vessels 3-5 in the field of view.

In the middle departments -2-4 in the field of view.

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

Elastic fibers: located parallel to the bundles of collagen fibers.

Glycosaminoglycans: dominated by chondroitin sulfates.

[1], [2], [3], [4], [5], [6]