Hypertrophic and Keloid Scars

Overview

Definitions

A hypertrophic scar Scar Dermatologic Examination (HS) is a benign Benign Fibroadenoma exuberant overgrowth of fibro-collagenous tissue. An HS occurs in an area of injury and grows rapidly, but does not go beyond the boundaries of the wound and tends to regress.

Keloids are defined as a benign Benign Fibroadenoma overgrowth of fibro-collagenous tissue, occurring in an area of dermal injury or chronic inflammation Chronic Inflammation Inflammation (rarely spontaneously). Unlike HSs, keloids continue to enlarge and grow beyond the original boundaries of the injury.

Epidemiology

HSs:

• 5%–70% of surgical patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
  • Up to 90% after deep burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns
  • Higher in people with dark skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
• More commonly develop after thermal or traumatic injury involving deep layers of the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions, or in chronically infected healing wounds

Keloids:

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency varies in different racially ethnic groups/ skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions types:
  • Higher predisposition in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with darker skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions complexion; however, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis content is not the determining factor:
    • White albino prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 0%
    • African albino prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 7.5% 
    • African non-albino prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 8.3%
  • Individuals of Hispanic and African ancestry: 5%–16% 
  • Whites: < 1%
• Site-specific differences:
  • Head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess surgical patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • African Americans: 0.8%
    • Caucasians: 0.1%
  • Women after cesarean section:
    • African Americans: 7.1%
    • Caucasians: 0.5%
• Familial keloids: 3%–4% of all keloids
• M:F = 1:1 
• More common in younger people (20–30-year-olds)

Etiology

• Multiple genetic factors involved, both in ethnic and familial forms:
  • Multiple, yet-to-be-defined genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure appear to be involved in keloid formation.
  • Familial forms have various inheritance patterns, with variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables penetrance Penetrance The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. Familial Juvenile Polyposis.
• Multiple local and individual factors induce hypertrophic scarring Hypertrophic Scarring Acne Vulgaris and keloid formation:
  • Local mechanical tension, infection
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension associated with severe keloids

Pathophysiology

Altered wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing causes an imbalance between an increased synthesis Synthesis Polymerase Chain Reaction (PCR) of collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology and extracellular matrix (ECM) and decreased degradation of collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology and ECM. 

• Altered (excessive) ECM synthesis Synthesis Polymerase Chain Reaction (PCR) in the 3rd phase of normal wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing (after inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and granulation Granulation Wound Healing tissue):
  • Increased fibroblast proliferation and collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology synthesis Synthesis Polymerase Chain Reaction (PCR)
• Over-expression of growth factors:
  • Transforming growth factor-beta (TGF-β)
  • Vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing 
  • Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology growth factor
• Decreased production of molecules that promote matrix breakdown (e.g., matrix metalloproteinases):
  • Increased platelet-derived growth factor receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis
  • Activated insulin-like growth factor-1
  • Decreased apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage rate of fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis

Pathology

HSs

• Pathology, gross: elevated scar Scar Dermatologic Examination that stays within the confines of initial injury borders
• Pathology, microscopic:
  • Thin, well-organized, wavy type III collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology bundles oriented parallel to the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions surface 
  • Many myofibroblasts 
  • Abundant acidic mucopolysaccharides Mucopolysaccharides Heteropolysaccharides which contain an n-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1, 4- and 1, 3-linkages consisting of either n-acetylglucosamine or n-acetylgalactosamine. Basics of Carbohydrates

Keloids

• Pathology, gross: elevated scar Scar Dermatologic Examination that extends beyond the borders of the initial injury, with invasion into the surrounding skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
• Pathology, microscopic:
  • Disorganized, large, thick, dense (“glassy”) type I and III hypocellular collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology bundles 
  • Few myofibroblasts
  • Poorly vascularized, dilated blood vessels 

Differences

Clinical Presentation

Diagnosis and Management

Diagnosis

• Clinical diagnosis, based on:
  • History
  • Scar Scar Dermatologic Examination shape and size
  • Growth pattern
• If uncertain, a skin biopsy Skin Biopsy Secondary Skin Lesions is performed to exclude other serious conditions.

Management

• Treatment of HSs has better success:
  • Intralesional corticosteroids Corticosteroids Chorioretinitis (or tapes and plasters for smaller scars)
  • Surgical resection, with or without skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions grafting or application of fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis glue scaffold containing autologous fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis and keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions
• Treatment of keloids is non-standardized and often ineffective, but moderate success can be achieved by using 1 or more therapies, including:
  • Corticosteroid injections (or tapes, plasters for small keloids)
  • Silicone gel sheeting
  • Pressure therapy
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
  • Cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma
  • Laser therapy Laser Therapy The use of photothermal effects of lasers to coagulate, incise, vaporize, resect, dissect, or resurface tissue. Glaucoma
  • Intralesional fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat
  • Immunomodulators (e.g., topical imiquimod)
  • Excision to debulk the scar Scar Dermatologic Examination (possible skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions grafting if the area is well vascularized): Adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination therapy is necessary or the keloid will recur, often growing to a larger size.

Prevention

For persons with a history of hypertrophic or keloid scarring Scarring Inflammation: 

• Avoid unnecessary trauma, including minor cosmetic procedures (e.g., ear piercing, removal of benign Benign Fibroadenoma skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions). 
• Acne or any skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Treat early.
  • Avoid chronicity.
• Acne keloidalis nuchae:
  • Avoid closely fitting caps or coverings.
  • No short haircuts or close shaves
  • Practice good topical hygiene with antimicrobial (chlorhexidine or benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum–based) cleansers/shampoos.
• After necessary surgery:
  • Keep the wound moist and covered.
  • Avoid stretching tension on the wound.
  • Avoid sun exposure to decrease hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi.

Differential Diagnosis

• Nodular scleroderma Scleroderma Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma (NS): rare variant of scleroderma Scleroderma Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma usually involving the chest, back, neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, and proximal portion of extremities, and is characterized by multiple firm, non-tender nodules or plaques with a histologic appearance similar to a keloidal scar Scar Dermatologic Examination. Nodular scleroderma Scleroderma Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma usually occurs with systemic sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor and with typical laboratory findings of antinuclear antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions in a homogenous pattern (titer 1:320) and positive anti-Scl70.
• Dermatofibrosarcoma protuberans (DFSP): rare cutaneous sarcoma that presents as a slowly growing plaque Plaque Primary Skin Lesions or nodule Nodule Chalazion. Histology shows uniform spindle cells Spindle Cells Acoustic Neuroma in long fascicles arranged in parallel to the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions, often showing a storiform pattern. Immunohistochemistry Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Myeloperoxidase Deficiency (CD34+) and molecular studies (t(17;22)) can support the diagnosis.
• Giant cell fibroblastoma (GCF): rare, subcutaneous low-grade sarcoma of childhood, considered to be a juvenile form Juvenile Form Spinal Muscular Atrophy of DFSP, with spindle-shaped fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis and multinucleated sarcomatous cells.
• Lobomycosis: chronic tropical fungal infection of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess, seen in Latin America. Presents as keloid-like nodules or plaques on exposed skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions. Diagnosis is easily made by biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma.