Keloid

Abnormal fibroproliferative scar that grows beyond the margins of the original wound, does not regress, and tends to recur after excision. Excess type I and III collagen is deposited in thick, hyalinised bundles, with raised fibroblast activity driven by TGF-beta, VEGF and other growth factors.

• Occurs in about 5 to 15% of wounds in predisposed people. Incidence is highest in people with darker skin (up to 15 to 20% in some African and Asian populations, 5 to 10 times higher than in lighter skin), in the age range 10 to 30, and in those with a family history (autosomal dominant pattern with variable penetrance, several susceptibility loci).
• Triggers: surgical incisions, trauma, burns, piercings (earlobes), acne, vaccination sites, insect bites, folliculitis, varicella and herpes zoster scars, and tattoos. Sites with high skin tension and a high keloid rate include the sternum, shoulders, upper back, deltoid, earlobes, jawline and suprapubic area. Eyelids, palms, soles and genitals rarely form keloids.
• Lesions can develop weeks to a year after injury, and may enlarge for years.
• Associations: Rubinstein-Taybi syndrome, Ehlers-Danlos syndrome and Goeminne syndrome (rare). Hormonal activity (puberty, pregnancy) can worsen lesions.

• Firm, rubbery, shiny, raised, pink to purple or dark brown nodule or plaque extending beyond the original wound edge, often with claw like or irregular lateral extensions. It is hairless and does not regress.
• Symptoms: itch (common), tenderness, burning, pain, and tightness. Large lesions limit movement across joints. The chest and shoulder lesions are most itchy and painful.
• Size varies from a few millimetres to more than 10 cm.
• Differential diagnosis: hypertrophic scar (stays within the wound, may regress in 1 to 2 years), dermatofibroma, dermatofibrosarcoma protuberans (slowly enlarging plaque, can arise in a scar, confirm with biopsy), scar sarcoidosis, cutaneous lymphoma, foreign body granuloma, acne keloidalis nuchae, sclerosing basal cell carcinoma, and lobomycosis or mycotic lesions.
• Complications: pain, itch, restricted motion, cosmetic and psychological distress, ulceration, infection and, rarely, malignant change (squamous cell carcinoma in chronic ulcerated lesions).

• Clinical, with the history of an earlier injury and growth beyond the wound edge.
• Biopsy for atypical, rapidly growing, ulcerated or recurrent lesions, to exclude dermatofibrosarcoma protuberans and other tumours. Keloid histology shows thick, glassy, eosinophilic collagen bundles and a lack of a nodular pattern.
• Ultrasound (high frequency) can define thickness and depth for planning.
• Ask about previous keloids, family history, and skin type, and record location, size, symptoms and tension on the lesion.

• Prevention in people with a history of keloids (the best treatment):
  • Avoid elective surgery, piercings and tattoos in high risk sites.
  • Treat acne and infection early.
  • Surgery with minimal tension, meticulous haemostasis, layered closure, incisions along skin tension lines, and avoiding sternal and deltoid incisions where possible.
  • Silicone gel or sheeting started as soon as the wound has epithelialised (usually 2 weeks), worn for 12 to 24 hours daily for 2 to 3 months.
  • Pressure garments (24 to 30 mmHg) for 23 hours a day for 6 to 12 months after burns, and pressure clips on earlobe wounds for 6 to 12 months.
  • Triamcinolone injection into the fresh wound at suture removal in high risk patients.
  • Sun protection of the scar with SPF 30 or more for 12 months.
• First line treatment:
  • Intralesional triamcinolone acetonide 10 to 40 mg/mL, injected into the body of the lesion (not the surrounding skin) with a 27 to 30 gauge needle and Luer lock syringe, until the lesion blanches, every 4 to 6 weeks for 3 to 6 sessions. Maximum about 40 mg per session in adults, up to 120 mg in large lesions under supervision. Use 10 mg/mL for the face and thin skin. Pain is reduced by mixing with lidocaine 1% and by pre-cooling. Response is about 50 to 100%, with recurrence in 9 to 50% at 5 years. Side effects: atrophy, telangiectasia, hypopigmentation (marked in dark skin), skin necrosis, menstrual changes and, rarely, Cushingoid effects in repeated large doses.
  • Silicone sheeting or gel, 12 to 24 hours daily for at least 3 months, as an adjunct.
  • Cryotherapy (contact or intralesional) with liquid nitrogen: 1 to 2 freeze thaw cycles of 10 to 30 seconds, every 3 to 4 weeks for 3 to 6 sessions. It shrinks small and moderate lesions, and may be combined with intralesional steroid. It causes permanent hypopigmentation, so it is avoided in dark skin unless pigment loss is accepted.
• Second line and combination injections:
  • 5-fluorouracil 50 mg/mL intralesional, 0.1 to 0.3 mL per cm of lesion, weekly to monthly for 3 to 6 sessions, alone or mixed with triamcinolone in a ratio of 9 parts 5-fluorouracil to 1 part triamcinolone 40 mg/mL. Pain, ulceration and pigment change occur. Avoid in pregnancy.
  • Verapamil 2.5 mg/mL intralesional, 0.5 to 1 mL per cm, monthly for 3 to 6 sessions, with fewer side effects but lower response.
  • Bleomycin 1.5 IU/mL, intralesional by multi puncture technique, every 4 weeks, with risk of necrosis and pigment change (evidence limited).
  • Botulinum toxin type A 20 to 70 units per lesion (evidence limited).
  • Interferon alfa-2b 1 million IU per cm intralesional (rarely used, because of cost and flu like side effects).
  • Imiquimod 5% cream nightly for 8 weeks after excision (evidence limited).
• Surgical excision: excision alone recurs in 45 to 100%, so it should be combined with adjuvant therapy:
  • Intramarginal or core excision, leaving a rim of keloid, with minimal tension closure, followed by intralesional triamcinolone at the time of surgery and at 4 to 6 weeks.
  • Excision plus postoperative superficial radiotherapy or electron beam: total 15 to 20 Gy in 2 to 4 fractions started within 24 to 72 hours of surgery (for example 8 Gy in 2 fractions or 5 Gy in 3 fractions). Recurrence falls to about 10 to 25%. Radiotherapy is used for resistant lesions in adults only, not in children, over the thyroid, breast or gonads, and its benefit must be weighed against a small theoretical cancer risk.
  • Flap, skin graft, or earlobe wedge excision with a pressure clip for large lesions.
  • Laser: pulsed dye laser 585 to 595 nm for erythema and itch, every 4 to 8 weeks for 3 to 6 sessions, with fractional carbon dioxide or erbium laser enabling steroid delivery. Ablative lasers alone can worsen lesions.
• Symptoms: topical capsaicin 0.025 to 0.075% cream, antihistamines (cetirizine 10 mg daily), gabapentin 300 mg increased to 900 to 1800 mg daily in divided doses for neuropathic pain, and hydrocolloid dressings.
• Special groups:
  • Children: use silicone, pressure and low dose triamcinolone. Avoid radiotherapy and 5-fluorouracil.
  • Pregnancy: lesions often enlarge. Use silicone and pressure. Defer injections of 5-fluorouracil, bleomycin and interferon. Triamcinolone is acceptable for short use if essential.
  • Dark skin: warn of pigment loss with steroid injection and cryotherapy.
  • Diabetes: control glucose, and check skin integrity before injections.
• Follow up: review every 4 to 6 weeks during injections, and then at 6, 12 and 24 months for recurrence. Refer to dermatology or plastic surgery for large, symptomatic, recurrent, joint restricting or suspicious lesions.