Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature.

Jean Louis Alibert (1768-1837) described these lesions in 1806 and called them cancroide. Later he changed the name to cheloide to avoid the connotation of cancer. The word is derived from the Greek chele, meaning crab's claw, and the suffix -oid, meaning like. According to Kaposi, Retz may have described keloids in 1790, when he wrote of a cicatricial tumor of supposed spontaneous origin which he names dartre de graisse. The customs of the Yorubas, a tribe from Nigeria, included facial markings and ear piercing. They described the familial occurrence and delayed presentation of keloids as early as 800 A.D.

Several factors affect reported incidences of keloids, including age, sex, race, anatomic location, and ritual scarring. Reported incidence ranges from 16% among adults in Zaire to 0.09% in England. Blacks form keloids more often than whites, with reported incidence ratios ranging from 2 to 1 and 19 to 1. According to Kelly, the tendency to form keloids does not appear to vary directly with the intensity of skin pigmentation.

Climate may play a role. Europeans living in the tropics form keloids more frequently than those living in temperate zones. According to some, the male to female prevalence is equal. Yet other investigators report a higher incidence in females, though this may reflect a greater cosmetic concern or a greater number of ear piercings. The average age of patients at the time of treatment is 25.8 years. Keloids have been observed in infants and adults over the age of 70.

The etiology of keloids is unknown. Though many associations exist, both anecdotal and statistically significant, none has shown a causal relationship. At present, no good models exist. Predisposing factors include: trauma, skin tension, infection, autoimmune phenomena, and hormonal factors.

In most patients trauma is the main or singular provoking factor. Associated cutaneous trauma includes abrasions, incisions, insect bites, chemical and thermal burns, acne and chicken pox. Many keloid-forming patients suffer trauma to the lips, palms of the hands, or more often to the soles of the feet, without forming keloids. This observation led investigators to postulate that these areas are spared because they lack sebaceous glands. Osman and associates hypothesized the "sebum autoimmune mechanism." This postulates that sebum is secreted intradermally after trauma; this sebum then acts as an antigen to trigger an autoimmune granulomatous response.

Keloids may follow bacterial or viral infections. Cutaneous lesions of acne, vaccinia, smallpox, and herpes varicella-zoster can lead to keloids.

Keloids have been associated with many hormones, alone or in combination. Acromegalics are highly susceptible to keloid formation. Keloids seem to grow during pregnancy and seldom occur before puberty. According to Ford et al, keloid scars demonstrate a higher level of androgen binding than surrounding normal tissue or hypertrophic scars. This is interesting in that circulating androgen concentrations rise during pregnancy. The chest upper back and neck are areas predisposed to keloids, and these areas have a higher rate of dihydrotestosterone metabolism.

The associations of keloids with acromegaly, puberty, pregnancy and hyperthyroidism suggest that the pituitary may play a role. In states of increased pituitary activity there is often associated hyperpigmentation due to concomitant increased MSH (melanocyte stimulating hormone) production. Some propose that this increased level of circulating MSH may cause keloids.

Certain areas of the body are predisposed to keloids. Some have proposed that areas of increased skin tension such as the chest and back are at risk. Others cite the presence of sebaceous glands, as on the chest or around the ears or neck, as the predisposing factor. There is a familial tendency for keloid formation. Both autosomal recessive and autosomal dominant patterns have been reported.

Keloids are masses of scar tissue, usually associated with trauma, which extend beyond the original injury. They usually project above the surrounding skin, but seldom extend deep to the dermis. They are usually asymptomatic, but can be tender or pruritic. They rarely ulcerate. Keloids are devoid of hair and other adnexa. Spontaneous regression of keloids is rare, and is associated with advanced age. These lesions may be pedunculated or sessile; those in the head and neck tend to be pedunculated. They are no well-documented cases of malignant degeneration of an unirradiated keloid.

The differential diagnosis of keloids is primarily hypertrophic scars. Keloids can be distinguished from hypertrophic scars which do not extend beyond the limits of the original trauma and usually regress within 18 months. Another entity which occurs in the head and neck and may resemble a keloid is allergic contact dermatitis secondary to earrings. However, histopathology of these lesions reveals lymphocytic infiltrates and lymphoid follicles.

J. Blake Goslen lists the following five stages of wound repair: vascular phase, inflammatory phase, re-epithelialization, granulation tissue formation, and matrix and collagen remodeling. The final phase of wound healing, matrix and collagen remodelling, begins as water is resorbed from the scar due to the replacement of hyaluronic acid by proteoglycans. Cross-linking of collagen fibers proceeds by lysyl oxidase. Type III collagen is catabolized and replaced by type I, and the collagen bundles are reoriented to lie parallel to the skin surface. The metabolic aberration which leads to keloid formation occurs in this late phase of scarring when keloids fail to mature and become compact.

The microscopic differentiation between keloids and hypertrophic scars can be difficult. In contrast to hypertrophic scars, keloids show thick, glassy, pale-staining collagen bundles. They also exhibit abundant mucinous ground substance, few fibroblasts, and no foreign body reactions, unlike hypertrophic scars. Blackburn and Cosman outline these criteria in their landmark article in 1966. The value of these criteria is that they are predictive of clinical outcome. Sixty percent of scars classified as keloids recurred, while only 10% of hypertrophic scars recurred.

Keloids differ from hypertrophic scars in osmotic pressure, metabolic activity, and collagen turnover as reflected in the local concentrations of sodium, magnesium and calcium respectively. Keloid collagen is thin and irregular and reveals cross-striations by electron microscopy, suggesting that it is immature. Also, keloids have a higher content of water and soluble collagen than normal skin. Keloids are deficient in lymphatics and associated elastic fibers. These qualities are true of early hypertrophic scars as well, but after seven months the two diverge as the hypertrophic scars normalize their water and collagen content.

The activity of Proline hydroxylase is markedly elevated in both hypertrophic scars and keloids when compared to normal scars. Collagen degradation appears to be normal or elevated. Serum alpha-globulins may explain why keloids accumulate collagen when the relative rates of synthesis and degradation appear normal in vitro. Patients with keloids have normal plasma concentrations of alpha-globulins, but increased deposition of alpha-globulins, alpha-1-antitrypsin, and alpha-2-macroglobulins in the keloid tissue. These substances are all known to inhibit the activity of collagenase. Intralesional injection of triamcinolone causes a reduction in local alpha-1-antitrypsin deposits. Steroid injections may reduce the size of keloids by reducing collagenase inhibition.

Drs. Appling, O'Brien, Johnston, and Duvic investigated transforming growth factor beta and found that together with vitamin C, it enhanced synthesis of RNA for collagen I and III, though only type I showed an increase in protein synthesis. Interestingly, transforming growth factor beta and ascorbic acid also increase the local concentration of protease inhibitors.

Therapy includes prevention, surgery, radiation therapy, steroid injections, pressure therapy, and laser therapy. Principles of prevention in keloid formers which apply to the head and neck include: withholding nonessential cosmetic surgery, closing all wounds with minimal tension (i.e., making incisions along Langer's lines), and the use of pressure garments for 4 to 6 months after injury.

Many surgical techniques have been applied to the problem of keloids either alone or in combination with other techniques. Surgery alone has shown a high recurrence rate. Lawrence reviewed seven studies which reported cure rates of 7% to 55%, and many of these studies had limited long-term follow-up.

There are only two cases of local cutaneous malignancy in patients who received irradiation for keloids, yet this association makes many shy away from radiotherapy. Newer studies, such as they by Levi et al, show response rates greater than 80% for postexcisional irradiation with 1000 to 2000 rads.

Hollander first reported promising results with steroid injections in 1961 using triamcinolone. The mechanism by which steroids reduces keloids is unknown but may involve increased collagenase production or decreased local alpha-s-macroglobulin concentrations.

Triamcinolone acentonide (Kenalog or Aristacort) in concentrations of 10mg - 40mg per ml may be used. This may result in transient hypopigmentation lasting 6 to 12 months. Clinically it is important to note that early keloids respond better to steroid injection, perhaps because steroids fail to induce collagenase production in older fibroblasts. Six studies published between 1961 and 1977 , showed significant objective response rates to steroids of 50% to 100%. It must be noted however, that response does not denote cure, and changes such as flattening, softening or an overall decrease in size may be considered a response. This may essentially mean trading a keloid for a hypertrophic scar.

Studies of surgery plus steroid injection had results no better than steroid injection alone. Yet, for large lesions, one may be able to produce a smaller controlled lesion by combining these methods.

Pressure therapy alone or as an adjunct to surgery effectively flattens and softens lesions. Compliance is a problem. Pressure earrings are convenient, but pressure dressing covering other areas of the head or neck are bulky and awkward.

Neither CO2 nor Nd:YAG prevents keloid recurrence unless combined with local steroid therapy. In a study by Strucker and Shaw which showed an 85% control rate, fewer than one in four keloids were controlled with laser therapy alone. A study by Stern and Lucente showed a recurrence rate of 70% with laser therapy alone; this is at least equal to the recurrence rate following sharp excision alone.

In summary, the clinical diagnosis of keloids is based upon persistence for greater than six months and spread beyond the site of original trauma.

Histology of keloids reveals thick collagen bundles, abundant ground substance, few fibroblasts, and few if any foreign body reactions.

Prevention must be the primary therapy. The most common treatment is a combination of cryotherapy, intralesional steroids and pressure devices, with surgery reserved for resistant lesions. Local cryotherapy with liquid nitrogen is used as an adjunct. It causes local anesthesia for subsequent injections and causes local edema which softens these otherwise dense lesions to facilitate injection.

Case Presentations

A 19-year-old man presents with a 2-year history of gradually enlarging scars on his left earlobe.

The patient had his ears pierced, once on the right and three times on the left. The problematic scars are pruritic but not painful. The patient has no other pathological scarring. On examination, two of the holes in the left ear lobe are now obliterated by keloid scars of 0.5 cm and 0.9 cm. The bulk of these scars is medial to the lobule.

The patient is being treated with serial local injections of triamcinolone acetonide, 10 mg/ml every 3 weeks, with noticable softening and a decrease in the bulk of the lesions.

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