In-Service Exam
Wound Healing Keloids - 2001





Which of the following is the most likely result following the intralesional injection of corticosteroids for treatment of keloids?

(A) Absence of adverse effects on the surrounding tissues
(B) Decreased risk for malignant degeneration
(C) Decreased risk for recurrence
(D) Lack of effectiveness on the connective tissue composition of the keloid
(E) Symptomatic relief of itching and burning

The correct response is Option E.

Intralesional corticosteroid injections are among several therapies used for treatment of keloids. Other therapeutic modalities include application of occlusive silicone dressings, use of compressive pressure earrings or dressings, interferon therapy, radiation therapy, cryosurgery, and laser or surgical excision. None of these treatments have been shown to be totally effective; however, corticosteroids have been shown to relieve the itching and burning symptoms associated with the keloids, as well as to decrease the collagen content of the keloids and subsequently decrease their size. Excision performed concomitantly with injection of corticosteroids will reduce the rate of recurrence to 30% to 50%. Low-dose radiation therapy administered postoperatively is associated with a similarly reduced rate of recurrence.

References
1. Berman B, Flores F. The treatment of hypertrophic scars and keloids. Eur J Dematol. 1998;8:591-595.
2. Sclafani AP, Gordon L, Chadha M, et al. Prevention of earlobe keloid recurrence with postoperative corticosteroid injections versus radiation therapy: a randomized, prospective study and review of the literature. Dermatol Surg. 1996;22:569-574.

Which of the following is the most likely mechanism of action of silicone sheeting/silicone gel pads in enhancing scar maturation?

(A) Decreasing wound tension
(B) Deregulating cellular integrins
(C) Enhancing epidermal contact inhibition
(D) Increasing the static electronegative field
(E) Maintaining regulated wound temperature

The correct response is Option D.

Silicone sheeting and silicone gel pads are used to treat hypertrophic or immature scars and keloids. Although their exact mechanism of action is unknown, some surgeons postulate that their positive effect is associated with the generation of an increased static electronegative field by the silicone. This mechanism of action results in favorable wound effects. Other theories propose that the wound-healing mechanism is related to the decreased oxygenation, sustained pressure, or hydrating effects of silicone oil resulting from the use of these products.

Silicone sheeting and gel pads have not been shown to decrease wound tension, affect epidermal contact inhibition, or regulate intracellular integrins or wound temperature.

References
1. Berman B, Flores F. The treatment of hypertrophic scars and keloids. Eur J Dermatol. 1998;8:591-595.
2. Hirshowitz B, Lindenbaum E, Har-Shai Y, et al. Static-electric field induction by a silicone cushion for the treatment of hypertrophic scars. Plast Reconstr Surg. 1998;101:1173-1183.

Which of the following impairs the process of epithelialization during wound healing?

(A) Basic fibroblast growth factor
(B) Epidermal growth factor
(C) Isotretinoin
(D) Keratinocyte growth factor
(E) Tretinoin

The correct response is Option C.

Isotretinoin is the only agent of those listed that impairs epithelialization instead of promoting it. Isotretinoin (13-cis retinoic acid, or Accutane) is a retinoid, one of a family of vitamin A-related agents. Because of its antikeratinization effect, which results in thinning of the stratum corneum and decreased activity of skin appendages such as sebaceous glands, as well as its effect on wound epithelialization, it is used in the treatment of cystic acne. In addition, patients who have been taking isotretinoin experience delayed or poor wound healing following chemical peeling or laser skin resurfacing because of the effect on wound epithelialization. Therefore, it is recommended that isotretinoin be discontinued a minimum of one year before chemical peeling or laser peeling is performed.

Basic fibroblast growth factor is a polypeptide and a member of the family of fibroblast growth factors (FGF). This agent stimulates important aspects of wound healing, including angiogenesis, collagen and collagen matrix syntheses, wound contraction, and epithelialization.

Epidermal growth factor is a polypeptide FGF that affects endothelial cells, fibroblasts, and smooth muscle cells. Because epithelial cells have been shown to have the greatest number of receptors for epidermal growth factor, the primary effect of epidermal growth factor is believed to be promotion of epithelialization.

Keratinocyte growth factor is produced by fibroblasts and also primarily affects epithelialization; only epithelial cells have keratinocyte growth factor receptors. Delayed wound healing has been reported in transgenic animals that lack this signaling receptor.

Although tretinoin is also classified as a retinoid, its effects are far different than isotretinoin. Tretinoin (all-trans-retinoic acid, Retin-A) promotes epithelialization by stimulating mitotic activity and decreasing the turnover of follicular epithelial cells. As a result, tretinoin is often used as a pretreatment in patients undergoing chemical peeling and laser skin resurfacing to accelerate wound healing. Other conditions for which tretinoin has proved beneficial include skin aging, acne vulgaris, and dysplastic nevus syndrome, as well premalignant and malignant tumors such as actinic keratosis, carcinoma in situ, and superficial basal cell carcinoma.

References
1. Glat PM, Longaker MT. Wound healing. In: Aston SJ, Beasley RW, Thorne CH, eds. Grabb & Smith's Plastic Surgery. 5th ed. Philadelphia, Pa: Lippincott-Raven; 1997:5-7.
2. Siftan D, ed. Physician's Desk Reference. 54th ed. Montvale, NJ: Medical Economics Corp; 2000:2063-2065.

Which of the following is the predominant type of collagen found in basement membrane?

(A) Type I
(B) Type II
(C) Type III
(D) Type IV
(E) Type V

The correct response is Option D.

Type IV collagen is the predominant collagen in basement membrane. In contrast, type I collagen is most often found in normal, mature skin, as well as in tendon and bone. Type II collagen is present in hyaline cartilage and the tissues of the eye. Type III collagen is located in the papillary dermis, arteries, intestinal walls, and uterus. In addition, hypertrophic and immature scars can contain as much as 30% type III collagen. Type V collagen is also found within the basement membrane in lesser amounts than type IV collagen.

References
1. Bailey AJ, Bazin S, Sims TJ, et al. Characterization of the collagen of human hypertrophic and normal scars. Biochem Biophys Acta. 1975;405:412.
2. Prockop DJ, Kivirikko KI, Tuderman L, et al. The biosynthesis of collagen and its disorders. N Engl J Med. 1979;301:13.

Which of the following sites is most susceptible to the development of a keloid following injury?

(A) Eyelid
(B) Genitalia
(C) Upper arm
(D) Palm
(E) Sole

The correct response is Option C.

Although keloids can occur in persons of any race, they are most frequently seen in dark-skinned persons. Keloids are most likely to develop on the face, cheek, earlobe, shoulder, upper arm, and anterior chest; in contrast, they are rarely seen on the eyelid, cornea, umbilical cord region, palm, genitalia, or sole. The origin of this regional susceptibility is unknown.

References
1. Ford T, Widgerow AD. Umbilical keloid: an early start. Ann Plast Surg. 1990;25:214-215.
2. LeFlore I, Antoine GA. Keloid formation on palmar surface of hand. J Natl Med Assoc. 1991;83:463-464.
3. Mullaney PB, Teichmann K, Huaman A, et al. Corneal keloid from unusual penetrating trauma. J Pediatr Ophthalmol Strabismus. 1995;32:331-334.
4. Niessen FB, Spauwen PH, Schalkwijk J, et al. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg. 1999;104:1435-1458.

In patients who exhibit allergic sensitivity to bovine collagen, which of the following types of immunologic response is most common?

(A) IgA antibodies
(B) IgD antibodies
(C) IgE antibodies
(D) IgG antibodies
(E) IgM antibodies

The correct response is Option D.

Anti-bovine collagen (Zyderm) antibodies are classified as IgG antibodies. Zyderm is a purified form of bovine collagen that consists of 95% type I collagen with 5% type II collagen. It is available in two concentrations, 35 mg/mL and 65 mg/mL, as well as in a glutaraldehyde cross-linked form known as Zyplast, which in theory degrades more slowly. Enzymatic processing is used to remove the nonhelical portion of the collagen molecule, thus reducing most of its associated antigenicity.

These various forms of injectable collagen are used for correction of depressed scars, shallow or soft acne scars, and fine facial rhytids associated with aging. Ice pick acne scars cannot be treated with collagen injections. In patients undergoing treatment, the collagen is injected intradermally in excess amounts, which are necessary to compensate for absorption of the saline component of the solution. Some of the injected collagen is lost over the next six to nine months as collagen breakdown occurs.

Because approximately 3% of all treated patients will have an allergic reaction to injectable bovine collagen, skin testing should be performed prior to any treatment. Following intradermal injection of a test dose into the volar forearm, the patient should be assessed 72 hours after injection and again at four weeks after injection, as any adverse changes noted at the test site may indicate an allergic reaction. This is defined as the onset of erythema, induration, tenderness, or swelling to any degree, with or without pruritus, that appears more than 24 hours after injection and/or persists longer than six hours.

Approximately 66% of those patients who are allergic to injectable collagen will have a positive reaction within 72 hours, while 33% will develop positive findings within four weeks. An additional 1% will have negative findings on skin testing but will subsequently develop an allergic reaction following injection. One study of those patients who had negative skin tests and subsequent allergic reactions showed that 56% developed a reaction following the first treatment, while 28% experienced the reaction after two treatments. All of the patients who exhibited allergic sensitivity developed IgG antibodies against bovine collagen. In contrast, 50% developed IgA antibodies; IgD, IgE, and IgM antibodies were not identified.

References
1. Baker TJ, Stuzin JM. Chemical peeling and dermabrasion: injectable collagen. In: McCarthy JG, ed. Plastic Surgery. Philadelphia, Pa: WB Saunders Co; 1990;1:781-784.
2. DeLustro F, Smith ST, Sundsmo J, et al. Reaction to injectable collagen: results in animal models and clinical use. Plast Reconstr Surg. 1987;79:581-594.
3. Frank DH, Vakassian L, Fisher JC, et al. Human antibody response following multiple injections of bovine collagen. Plast Reconstr Surg. 1991;87:1080-1088.
4. Hanke CW, Thomas JA, Lee WT, et al. Risk assessment of polymyositis/dermatomyositis after treatment with injectable bovine collagen implants. J Am Acad Dermatol. 1996;34:450-454.
5. Siegle RJ, McCoy JP Jr, Schade W, et al. Intradermal implantation of bovine collagen: humoral immune responses associated with clinical reactions. Arch Dermatol. 1984;120:183-187.

In normal wound healing, collagen synthesis and collagen breakdown typically reach a state of equilibrium approximately how many days after injury?

(A) 7
(B) 14
(C) 21
(D) 60
(E) 90

The correct response is Option C.

In normal wound healing, collagen synthesis and collagen breakdown typically reach a state of equilibrium approximately 21 days after initial injury. Collagen synthesis depends primarily on production of procollagen by fibroblasts. This procollagen is inserted into secretory vessels that move toward the cell surface. It then is cleaved into collagen at the level of the cell membrane, and the collagen is then released into the wound. Macrophages help to regulate collagen synthesis by producing growth factors that stimulate fibroblast proliferation and subsequent collagen production.

In collagen degradation, fibroblasts, granulocytes, macrophages, and other cells produce specific matrix metalloproteinases (MMP) at the wound site. The MMP family of zinc-dependent endopeptidases includes collagenase, gelatinase, and stromelysin. Several members of the MMP family have been linked to chronic wounds; these substances, such as MMP-2 and MMP-9, have been shown to be absent in acute wounds. A higher turnover of extracellular matrix is thought to contribute to the delayed healing or nonhealing seen in association with chronic wounds. Transforming growth factor-beta can be used to combat this; it has been shown to decrease MMP activity and increase the activity of MMP inhibitors.

References
1. Glat PM, Longaker MT. Wound healing. In: Aston SJ, Beasley RW, Thorne CH, eds. Grabb & Smith's Plastic Surgery. 5th ed. Philadelphia, Pa: Lippincott-Raven; 1997:5-7.
2. Peacock EE Jr, Cohen IK. Wound healing. In: McCarthy JG, ed. Plastic Surgery. Philadelphia, Pa: WB Saunders Co; 1990;1:161-185.