Pathophysiology and Prevention of Scar

Tissues

Deny budimanAchmad p

Hendrikus bollyJocliedian GL

The Anatomy of Human Skin

Epidermis (5 layers)Keratinocytes provide protective

properties.

Melanocytes provide pigmentation.

Langerhans’ cells help immune system.

Merkel cells provide sensory receptors.

Dermis (2 layers)Collagen, glycoaminoglycans, elastine,

ect.

Fibroblasts are principal cellular constituent.

Vascular structures, nerves, skin appendages.

Hypodermis (fatty layer)Adipose tissue plus connective tissue.

Anchors skin to underlying tissues.

Shook absorber and insulator.

Eight Functions of Human Skin

1. Protect underlying tissues from injury: mechanical, heat, cold, biological.

2. Prevent excess water loss.

3. Act as a temperature regulator.

4. Serve as a reservoir for food and water: adipose tissue

5. Assist in the process of excretion: H20, Salt, Urea, Lactic Acid.

6. Serve as a sense organ for cutaneous senses: pain, heat, cold, pressure, touch.

7. Prevent entrance of foreign bodies: microorganisms.

8. Serve as a seat of origin for Vitamin D.

Phases of Wound Healing

1. Clotting2. Vascular

Response3. Blood

coagulation4. Inflammation5. Formation of

new tissue6. Epithelialisation7. Contraction &

Remodeling

Physiological Stages

1.) Inflammatory Phase Initial response to injury Day 1-4 post injury Characterized by rubor, tumor, dolor, calor Platelet aggregation and activation Leukocyte (PMNs, macrophages) migration, phagocytosis

and mediator release Venule dilation Lymphatic blockade Exudative In wounds closed by primary intention, lasts 4 days In wounds closed by secondary or tertiary intention,

continues until epithelialization is complete

2.) Proliferative PhaseDay 4-42Fibroblast proliferation

stimulated by macrophage-released growth factors

Increased rate of collagen synthesis by fibroblasts

Granulation tissue and neovascularization

Gain in tensile strength

3.) Remodeling Phase6wks-1 yearIntermolecular cross-

linking of collagen via vitamin C-dependent hydroxylation

Characterized by increase in tensile strength

Type III collagen replaced with type I

Scar flattens

The stages of healing

Abnormal Wound Healing

KeloidHypertrophic scarContractureTrauma

Keloids overgrowth fibrous tissue after

healing of a skin injury. Tissue extends beyond the borders

of woundNot usually regress spontaneouslyRecur after excision 3 months to

years The first description of keloids

Egypt in 1700 BCE. 1806, Alibert cheloide chele, or crab's claw lateral growth of tissue

Keloids

Hypertrophic scars

Erythematous, pruritic, raised fibrous lesions

Not expand over border of initial injury

Partial spontaneous resolution After thermal injuries and other

injuries that involve the deep dermis 4 weeks after trauma

Hypertrophic

Scar

Hypertrophic Scar / KeloidHypertrophic Scars Keloids

Occur soon after injury or surgery. May not develop for many months after injury or surgery.

Usually flatten spontaneously with time.

Remain elevated and do not spontaneously resolve.

Limited to the area of the original tissue damage.

Not confined and may overgrow wound boundary.

Size related to the injury. A minor injury may produce a large lesion.

Occur with motion and tension. Independent of motion.

Usually occur across flexor surface, for example joints.

Commonly occur on ear lobes, shoulders, pre-sternal skin and upper back.

May be improved with appropriate surgery.

May be worsened with surgery.

Few collagen fibres; nodular structures containing fibroblastic cells, small vessels and collagen.

Large, thick collagen fibres in closely packed fibrils.

Contracturescars that cross joints or skin creases

at right angles are prone to develop shortening 

a serious functional consequence of excessive scar formation

occur when the scar is not fully matured, often tend to be hypertrophic, and are typically disabling and dysfunctional

 common after burn injury across joints or skin concavities.

Contracture

Contraction Vs Contracture

Contraction: centripetal movement of the whole thickness of surrounding skin reducing scar

Myofibroblasts: special Fibroblasts express smooth muscle and bundles of actin connected through cellular fibronexus to ECM fibronectin, communicate via gap junctions to pull edges of the wound

Contracture: the physical constriction or limitation of function as the result of Contraction (scars across joints, mouth, eyelid)

Burn/Keloid causing contracture

Trauma / Chronic WoundsTraumatic injuries can be sustained

from heat (burns) and cold (frostbite) and are often a combination of partial and full thickness injuries

Traumatic wounds are usually sustained in a dirty environment and contamination can lead to prolonged healing and a higher incidence of infection.

Lacerations and open injuries older than 24h

Trauma / Chronic Wounds

 Scar ClassificationMature Light-coloured and flat.Immature Red, sometimes itchy and painful, slightly elevated. Many will mature to

become flat and assume pigmentation similar to the surrounding skin, although they can be paler or slightly darker.

Widespread Stretched

Appear when the fine lines of surgical scars gradually become stretched and widened. Typically flat, pale, soft, symptomless scars often seen after knee or shoulder surgery. Stretch marks (abdominalstriae) after pregnancy are variants of widespread scars. No elevation, thickening, or nodularity which distinguishes them from hypertrophic scars.

Atrophic Flat and depressed below the surrounding skin. Generally small and often round with an indented or inverted centre. Commonly arise after acne or chickenpox.

Contractures Scars that cross joints or skin creases at right angles are prone to develop shortening or contracture. Occur when the scar is not fully matured. Often tend to be hypertrophic, and are typically disabling and dysfunctional. Common after burn injury.

Linear Hypertrophic

Red, raised and sometimes itchy. Confined to the border of the original surgery or trauma. Develops within weeks of surgery. May increase rapidly in size for 3-6 months and then, after a static phase, begin to regress. Mature to have an elevated, slightly rope-like appearance with increased width. Full maturation can take up to two years.

Widespread Hypertrophic

Common after a burn. A widespread red raised and sometimes itchy scar that remains within the borders of the original burn.

Minor Keloid A focally raised, itchy scar that extends over normal tissue. May develop up to one year after injury and does not regress without treatment. Surgical excision is often followed by recurrence.

Major Keloid A large, raised scar which may be painful or pruiritic. Extends over normal tissue and can continue to spread over many years.

Pathophysiology

variations of typical wound healing. typical wound equilibrium anabolic and

catabolic processes ( 6-8 weeks ) 30-40% strength

scar matures strength cross-linking of collagen fibers hyperemic and thickened subside gradually over months until a flat, white, pliable, possibly stretched, mature scar has developed.

Imbalance more collagen grows all directions elevated , hyperemic. keloid or hypertrophic scar.

Kischer and Brody collagen nodule unit of hypertrophic scars and keloids.

Collagen nodule high density of fibroblasts and unidirectional collagen fibrils in a highly organized and distinct orientation rich vasculature, high mesenchymal cell density, and thickened epidermal cell layer.

Clinically differentiate keloids from hypertrophic difficult in early phases of formation.

Histologic difference Keloid broad, dull, pink bundles of collagen

FrequencyOnly humans All age groups rarely found in newborns

or elderly persons Highest aged 10-20 years.Mortality/MorbidityMost sites cosmetic some can cause

contractures overlying a joint or in significant disfigurement if located on the face

Genetically HLA-B14, HLA-B21, HLA-Bw16, HLA-Bw35, HLA-DR5, HLA-DQw3, and blood group A

RacePolynesian and Chinese White persons are least commonly

affected.SexHigher in young females earlobe piercing Both sexes equally other age groups.Age10-30 years. Less frequently extremes of age,

increasing number of presternal keloids coronary artery bypass operations and other similar procedures now undertaken in persons in older age groups.

CLINICALHistoryNot cause symptoms tender,

painful, or pruritic, burning sensation. Origins of lesions

◦Keloids areas trauma past the areas above skin rarely into subcutaneous tissue.

◦Hypertrophic limited traumatized area regress 12-24 months not complete

Clinical findings of KeloidsSoft , rubbery and hard. Early lesions erythematous brownish

red paleDevoid hair follicles and adnexal glandsEnlarge rapidly months stop growing

stable or involute slightlyEars, neck, and abdomen pedunculatedCentral chest and extremities raised with

a flat surface, base wider than the top.Round, oval, or oblong with regular

margins clawlike configurations, irregular borders.

Joint contract.

Frequency of lesion sitesWhite persons Face cheek and earlobes Upper extremities, chest, presternal area,

neck, back, lower extremities, breasts, and abdomen.

Black persons Earlobes, face, neck, lower extremities,

breasts, chest, back, and abdomen.Asian persons, Earlobes, upper extremities, neck, breasts,

and chest.

CausesEnigma no specific gene or set of genes Trauma primary Foreign material, infection, hematoma, or

increased skin tension in susceptible individuals.

Lab StudiesBiopsy diagnosis

TREATMENT

Medical CareNo single therapeutic modality is

best Individual Prevention keyPrevention :

◦Avoid nonessential cosmetic surgery ◦Minimal tension surgical wound◦Incisions not cross joint spaces.◦Avoid midchest incisions◦ incisions follow skin creases

Standard treatments

Occlusive dressings silicone gel sheets and dressings, nonsilicone occlusive sheets, and Cordran tape. occlusion and hydration

Previous studies silicone occlusive 24 h/d, 12 months,

34%excellent, 37.5% moderate, and 28% no or slight improvement

semipermeable, semiocclusive, nonsilicone-based dressings 8 weeks, 60% flattening of keloids, 71% reduced pain, 78% reduced tenderness, 80% reduced pruritus, 87.5% reduced erythema, and 90% were satisfied with the treatment.

• Compression therapy pressure thinning Reduction cohesiveness of collagen

• Button compression, pressure earrings, ACE bandages, elastic adhesive bandages, compression wraps, spandex or elastane (Lycra) bandages, and support bandages.

60% of patients treated with these devices showed 75-100% improvement.

Corticosteroids• Intralesional injections • Reduce collagen synthesis reducing

production of inflammatory mediators and fibroblast proliferation

• Triamcinolone acetonide (TAC) 10-40 mg/mL/4-6 week Response 50-100%, recurrence 9-50% (+) excision, postoperative intralesional TAC reccurence < 50%.

• Complications atrophy, telangiectasia formation, and pigmentary alteration

New treatments intralesional interferon, 5-FU, doxorubicin, bleomycin, verapamil, retinoic acid, imiquimod 5% cream, tacrolimus, tamoxifen, botulinum toxin, TGF-beta3, and rhIL-10.

Interferon therapy • Alfa, beta, and gamma reduce

production of collagen types I, III, and VI mRNA.

• Alfa and Beta reduce glycosaminoglycans (GAGs) deposition of dermal collagen

• Increase collagenase activity Gamma modulates p53 apoptotic

pathway mutations hyperproliferation keloid formation

• Interferon injected into the suture line prophylactic for reducing recurrences.

5-Florouracil• Inhibits fibroblastic proliferation reduce

postoperative scarring • Effective hypertrophic scars and small

keloids. Doxorubicin (Adriamycin)• Irreversibly inactivates prolyl 4-

hydroxylase inhibit collagen alpha-chain assembly excessive scarring

Bleomycin • Injections necrosis of keratinocytes

with a mixed inflammatory infiltrate.

Tamoxifen, Synthetic nonsteroidal antiestrogen Inhibit proliferation of keloid fibroblasts

and their collagen synthesis in monolayer cultures.

Reduce TGF-alpha, and its isoform TGF-alpha1, production

Radiation therapyControversial some studies efficacy

and decreased recurrence rates safety ?

Surgical CareCryotherapyCryosurgical liquid nitrogen

microvasculature cell damage Possibility of reversible

hypopigmentation, pain and permanent depigmentation

51-74% total resolution, no recurrences

Laser therapyCarbon dioxide laser (10,600 nm)

dry surgical environment with minimal tissue trauma.

Recurrence rates 39-92% (+) postoperative injected steroids recurrence rates 25-74%.

Argon laser (488 nm), Nd:YAG laser (1064 nm), pulsed dye laser (585 nm)(treatment of choice)

Excisional surgeryLeast amount of soft tissue

minimize traumaClosure minimal skin tension

full- and split-thickness skin grafts

Remove source postoperative inflammation trapped hair follicles, foreign material, hematomas, or infectious areas.

Recurrence rates surgery alone range from 45-100%.

Effective combined with external radiation, steroid injection, pressure therapy, or a combination

Z-Plasty

LengthensReorients

FOLLOW-UPHigh rate of recurrence 1 year follow

up Close follow-up monitoringPreventionAvoid sharp traumaMinimize inflammation acne or

surgery.Complicationsinfection.PrognosisKeloids rarely resolve spontaneously Excision treatment alone recur

(>50%).

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