Excess Wound Healing

• Pathophysiology of excess scar production during wound healing
  • Excessive scarring results from an overabundance of collagen production by fibroblasts in the wound
  • There is increased production of:
    • Certain isoforms of TGF-B (Primary mediator) – TGFB1 and B2 increase angiogenesis (proliferation) and collagen deposition (maturation); also prevents collagen breakdown by inhibiting metalloproteinases (collagenase) and upregulating tissue inhibitors of metalloproteinase
    • Connective tissue growth factor (downstream signaling factor of TGF-B)
    • PDGF
    • Tissue inhibitors of metalloproteinases
  • Decreased production of
    • Fibroblast growth factor (FGF)
    • Metalloproteinases (collagenases)
    • IL-10
• Treatment options for keloids and hypertrophic scars
  • First line: Silicon gel
    • +/- pressure garment
    • +/- steroids
  • Second line: Steroids
    • +/- silicon
    • +/- cryotherapy
    • +/- 5-FU
  • Third line: Surgery
    • +/- steroids
    • +/- radiation therapy
    • +/- 5-FU

Excess healing	Description
Excessive scarring	Excess proliferation of fibroblasts and collagen due to dysregulation of the proliferative and maturation stage
Hypertrophic scar	Excess proliferation of fibroblasts and collagen leading to a raised scar that does not grow beyond the boundaries of the original lesion
Keloid	Excess proliferation of fibroblasts and collagen in typically small skin injuries leading to a raised scar that grows beyond the wound margins in a “claw-like” appearance
Exuberant granulation tissue	Formation of excessive amounts of granulation tissue (”proud flesh”)
Desmoid tumor	Fibrous tumors that occur during healing due to abnormal fibroblast proliferation in response to growth factors
Contracture	Contraction of wound edges caused by myofibroblasts. Occurs to a greater extent in healing by secondary-intention than primary intention

Excessive healing in different tissue

Site	Excess healing
Skin	Excessive scarring, keloids, contracture
Tendon	Frozen repairs
GIT or Urinary Tract	Strictures or stenosis
Solid organs	Cirrhosis, pulmonary fibrosis
Peritoneum	Adhesive disease

Keloid vs Hypertrophic scar

	Hypertrophic scar	Keloid
Genetics	Not familial	May be familial
Race	Not related to race	Black > white
Sex	F = M	F > M
Cause	Occur across areas of tension and flexor surfaces.	Abnormal fibroblasts within the wound as compared to normal dermis
Common site	Flexor surface, but can appear anywhere	Neck, chest, upper back, shoulders and ear lobes
Wound margins	Maintained, but rises above the skin level	Outgrows the wound margin
Histology	Increased type III collagen with parallel orientation of collagen fibres	Increased type I collagen with randomly oriented fibres
Symptoms	Mild pruritus, but relatively asymptomatic	Pain, pruritus, hyperesthesia
Response to treatment	Better	Less
Spontaneous regression	Often	Rare
Prevention	Preventable with appropriate surgical incision and wound care (for trauma and burns)	No preventable