Cutaneous Necrosis

Etiology

Cutaneous necrosis may occur with the injection of any sclerosing agent even under ideal circumstances and does not necessarily represent physician error. Fortunately, its occurrence is rare. Its cause may be the result of (1) extravasation of a sclerosing solution into the perivascular tissues, (2) injection into a dermal arteriole or an arteriole feeding into a telangiectatic or varicose vein, (3) a reactive vaso-spasm of the vessel, or (4) excessive cutaneous pressure created by compression techniques.

Extravasation

Extravasation of caustic sclerosing solutions may directly destroy tissue. The extent of tissue injury is related directly to both the concentration of the sclerosing solution and the quantity extravasated. As discussed later, different scleros-ing solutions have a greater or lesser ability to destroy tissue. Since the final clinical appearance of the skin may not be apparent for several days, therapeutic intervention must be undertaken as soon as possible in all cases.

Clinically, bright erythema is present in the skin overlying the extravasated solution. With certain extravasation injuries, the formation of epidermal blistering may occur but does not predict a partial-thickness injury, although it may precede eventual full-thickness necrosis.

During injection of an abnormal vein or telangiectasia, even the most adept physician may inadvertently inject a small quantity of sclerosing solution into the perivascular tissue. A tiny amount of sclerosing solution may be left in the tissue when the needle is withdrawn, and sclerosing solution may leak out of the injected vessel, which has been traumatized by multiple or through-and-through needle punctures. Rarely the injection of a strong sclerosing solution into a fragile vessel may lead to endothelial necrosis and rupture, producing a "blow-out" of the vessel and perivascular extravasation of sclerosing solution. Therefore injection technique is an important but not foolproof factor in avoiding this complication even under optimal circumstances.

Matting From Sclerotherapy

FIGURE 15.6 Typical telangiectatic matting (TM) in a 36-year-old woman. A. Left lateral thigh before sclerotherapy treatment. B. Three months after treatment of reticular veins with POL 0.75%. C. Six weeks after treatment of telangiectatic veins with POL 0.5%; note development of extensive TM. D. Six weeks later; note complete resolution of TM without treatment. (From Goldman MP. Adverse sequelae of sclerotherapy treatment of varicose and telangiectatic leg veins. In Bergan JJ, Goldman MP, eds. Varicose veins: Diagnosis and treatment. 1993. St Louis: Quality Medical Publishing.)

FIGURE 15.6 Typical telangiectatic matting (TM) in a 36-year-old woman. A. Left lateral thigh before sclerotherapy treatment. B. Three months after treatment of reticular veins with POL 0.75%. C. Six weeks after treatment of telangiectatic veins with POL 0.5%; note development of extensive TM. D. Six weeks later; note complete resolution of TM without treatment. (From Goldman MP. Adverse sequelae of sclerotherapy treatment of varicose and telangiectatic leg veins. In Bergan JJ, Goldman MP, eds. Varicose veins: Diagnosis and treatment. 1993. St Louis: Quality Medical Publishing.)

Hyperosmotic agents with an osmolality greater than that of serum (281 to 289 mOsm/L) can cause tissue damage as a result of osmotic factors. Epidermal necrosis even has occurred from extravasation of solutions containing 10% dextrose.25 HS 23.4% is a caustic sclerosing agent as dem onstrated in intradermal injection experiments. Clinically, small punctate spots of superficial epidermal damage occur at points of injection, especially when a small bleb of the solution escapes from the vein. However, subcutaneous injection of up to 1 ml of HS 23.4% (by mistake) in lieu of lidocaine into the neck or cheek has been reported to result in no adverse sequelae. However, the increasing frequency of cutaneous necrosis occurring after extravasation of inadvertent subcutaneous injection of HS has moved the Department of Health and Human Services and the product manufacturer (American Regent Laboratories, Inc.) to recommend that HS be stored only in pharmacies where all dilutions would be performed before dispensing. This would eliminate the possibility of an iatrogenic medication error outside the pharmacy (Mary Helenek, American Regent Laboratories, Inc., written communication, May 1990).

Experimentally, POL apparently is minimally toxic to subcutaneous tissue. Duffy26 has reported injecting 0.5 ml of a 3% solution of POL directly into his own forearm skin without the development of an ulceration. POL in sufficient concentration causes cutaneous necrosis. Solutions of POL greater than 1.0% may produce superficial necrosis with intradermal injection. This unfortunately occurred with the mistaken injection of 0.1 ml POL 5% solution into a leg telangiectasia 0.2 mm in diameter in our practice. This injection resulted in extensive overlying cutaneous necrosis that took eight weeks to heal. Therefore POL is not without the risk of cutaneous necrosis if a strong enough concentration is injected.

Although STS is more toxic to tissue than POL, with extravasation, concentrations above 0.25% usually are necessary to produce ulceration. Banning reported on the development of ulcerations in five of 4860 consecutive patients after telangiectasia were injected with STS 0.1% (presentation at the eighth annual meeting of the North American Society of Phlebology, Ft. Lauderdale, Fla, February 28, 1995). As discussed later, this probably represents injection into an arteriole.

Glycerin or chromated glycerin (CG) solutions have not been reported to produce cutaneous necrosis with extravasation. Duffy (personal communication, 1992) has shown that injection of full-strength CG will not produce cutaneous necrosis when it is injected into the mid-dermis. Histologic examination of his patient showed no evidence of dermal or epidermal damage.

Even when sclerotherapy is performed with expert technique, using the safest sclerosing solutions and concentrations, cutaneous ulceration may occur. Therefore it appears that extravasation of caustic sclerosing solutions alone is not totally responsible for this complication.

Arteriolar Injection

De Faria and Moraes27 have observed that one in 26 leg telangiectasias is associated with a dermal arteriole. Bihari and Magyar28 have found pulsatile flow in 68.9% of patients in 16 of 18 biopsies 2.5 x 1.5 cm taken from the pulsepositive telangiectasia in patients demonstrating arteriove-

nous microshunts. This gives a 61% incidence of AV microshunts in patients with leg telangiectasia. An expanded study of 155 patients with leg telangiectasia demonstrated a 72.2% incidence of pulsitile flow by the same group.29 The higher incidence found in the later two studies probably is caused by the larger biopsy specimens taken. Of the 22 Doppler-positive telangiectasia, 19 demonstrated AV microshunts on biopsy. Thus it is likely that rapid injection or large volume injection into leg telangiectasia that are associated with microshunts will force the sclerosing solution into the arterial circulation. It is our opinion that inadvertent injection into or near this communication is the most common cause of cutaneous ulcerations.

It has been shown by Duffy as well as our experience that when POL is injected intradermally to effect sclerosis of TM cutaneous ulceration does not occur, even with the injection of 0.5 ml of a 0.75% solution. However, we have noted the development of 3- to 6-mm diameter ulcerations in approximately 0.0001% of injections with POL 0.5%. Five consecutive ulcerations that appeared over the course of 12 months were excised. In these patients each cutaneous ulceration developed as the result of the occlusion of the feeding dermal arteriole. This produced a classic wedge-shaped arterial ulceration (see Figure 15.7). The Australian Polidocanol Open Clinical Trial at two years reported 43 ulcers on 32 legs after sclerotherapy treatment of varicose and telangiec-tatic leg veins on 12,544 legs, for an incidence of 0.23%.30 Therefore it appears that rare cases of small ulcerations may be unavoidable to some extent.

Interestingly, since we have been using glycerin solution in a 72% concentration mixed 2 : 1 with 1% lidocaine with or without epinephrine 1 : 100,000 we have not seen ulcerations at all. The safety of glycerin may be its high viscosity, which prevents the solution from flowing into arteriole connections. Alternatively, the epinephrine mixed into the solution may put the arteriolar portion of the AV anastomosis into spasm and/or the lidocaine portion may vasodilatate and protect the arteriolar portion of the AV anastomosis.

Vasospasm

Rarely after injection of the sclerosing solution an immediate porcelain-white appearance is noted at the site of injection. A hemorrhagic bulla usually forms over this area within two to 48 hours and progresses to an ulcer. This cutaneous reaction might represent an arterial spasm.

Vasospastic reactions of arteries occur in predisposed individuals for unknown reasons. This may occur even with puncture of the artery without injection of sclerosing solution. Thus small vessels, when irritated in susceptible patients, may spasm.

In an attempt to reverse the spasm, vigorous massage when the white macule appears usually prevents the devel

Sclerotherapy Cutaneos Necrosis

FIGURE 15.7 A. Low-power view showing skin ulceration and focal inflammation extending into the subcutaneous fat. A thrombosed vessel, most likely an artery, is present directly under the area of necrosis (hematoxylin-eosin; x25). B. Higher magnification of same area as in A, showing a thrombosed artery that caused the infarct. The arterial lumen is completely occluded by fresh thrombus (hematoxylin-eosin; x200). (From Complications of Sclerotherapy. In Sclerotherapy Treatment of Varicose and Telangiectatic Leg Veins, 4e. Goldman MP, Bergan JB, Guex JJ, eds. London: Elsevier. 2006.)

FIGURE 15.7 A. Low-power view showing skin ulceration and focal inflammation extending into the subcutaneous fat. A thrombosed vessel, most likely an artery, is present directly under the area of necrosis (hematoxylin-eosin; x25). B. Higher magnification of same area as in A, showing a thrombosed artery that caused the infarct. The arterial lumen is completely occluded by fresh thrombus (hematoxylin-eosin; x200). (From Complications of Sclerotherapy. In Sclerotherapy Treatment of Varicose and Telangiectatic Leg Veins, 4e. Goldman MP, Bergan JB, Guex JJ, eds. London: Elsevier. 2006.)

opment of ulceration. However, prevention of the ulceration with massage alone is not always successful. Massaging in a nitroglycerin ointment 2% is more likely to prevent the development of ulcerations in this setting. The major systemic action of nitrates is a direct reduction in venous smooth muscle tone. Nitrates also relieve spasm of angiographically normal and diseased arteries.

Arterial spasm also may explain the development of cutaneous ulceration upstream from the injection site (see Figure 15.8). In this latter case, 2 ml of POL 0.25% was injected into a feeding reticular vein (arrow, Figure 15.8). That was the only injection given to the patient in that sclerotherapy session. This also has been reported by Rabe, and was termed embolia cutis medicamentosa.31

Prevention

If extravasation of sclerosing solution occurs, the solution must be diluted as soon as possible. Hypertonic solutions should be diluted with copious amounts of normal saline solution. At least 10 times the volume of extravasated solution should be injected to limit osmotic damage.

Detergent sclerosing solutions of adequate strength also may be toxic to tissues. Dilution is again of paramount importance. Dilution with hyaluronidase in normal saline solution limits the extent and prevents development of cutaneous necrosis from 3% STS.32 Hyaluronidase (Wydase, lyophilized, 150 USP U/ml) enzymatically breaks down connective tissue hyaluronic acid. This is hypothesized to disrupt the normal interstitial fluid barrier to allow rapid diffusion of solution through tissues, thereby increasing the effective absorption. In addition to its enhanced dilutional

Skin Necrosis

FIGURE 15.8 Cutaneous necrosis 6 weeks after sclerotherapy with POL 0.25%. Note that 2 ml of solution was injected into a feeder vein approximately 10 cm distal to the necrotic area. (From Complications of Sclero-therapy. In Sclerotherapy Treatment of Varicose and Telangiectatic Leg Veins, 4e. Goldman MP, Bergan JB, Guex JJ, eds. London: Elsevier. 2006.)

FIGURE 15.8 Cutaneous necrosis 6 weeks after sclerotherapy with POL 0.25%. Note that 2 ml of solution was injected into a feeder vein approximately 10 cm distal to the necrotic area. (From Complications of Sclero-therapy. In Sclerotherapy Treatment of Varicose and Telangiectatic Leg Veins, 4e. Goldman MP, Bergan JB, Guex JJ, eds. London: Elsevier. 2006.)

ability, hyaluronidase may have an independent cellular preservation function.

Hyaluronidase injection improves skin flap survival.33 This has been postulated to occur through enhanced nutritive flow. Enhanced healing with resolution of painful induration was observed when 250 U of hyaluronidase was injected in an area where neoarsphenamine and oxophenarsine

Chapter 15/Complications and Adverse Sequelae of Sclerotherapy

Chapter 15/Complications and Adverse Sequelae of Sclerotherapy

Posterolateral Thigh Varicosities

FIGURE 15.9 Cutaneous ulceration on the posterolateral thigh. A. Three weeks after treatment with POL 0.5%. B. After 6 months. Treatment consisted of a duoderm dressing that was changed every 4 days until complete healing occurred in 5 weeks. Note the cosmetically acceptable stellate scar. (From Complications of Sclerotherapy. In Sclero-therapy Treatment of Varicose and Telangiectatic Leg Veins, 4e. Goldman MP, Bergan JB, Guex JJ, eds. London: Elsevier. 2006.)

FIGURE 15.9 Cutaneous ulceration on the posterolateral thigh. A. Three weeks after treatment with POL 0.5%. B. After 6 months. Treatment consisted of a duoderm dressing that was changed every 4 days until complete healing occurred in 5 weeks. Note the cosmetically acceptable stellate scar. (From Complications of Sclerotherapy. In Sclero-therapy Treatment of Varicose and Telangiectatic Leg Veins, 4e. Goldman MP, Bergan JB, Guex JJ, eds. London: Elsevier. 2006.)

(Mapharsen) were extravasated subcutaneously.34 Finally, hyaluronidase promotes wound repair in fetal skin, contributing to scarless repair of wounds by as yet unclear mechanisms.35 In summary, accelerated dilution, cellular stabilization, and wound repair properties of hyaluronidase appear useful in preventing cutaneous necrosis from inadvertent sclerosing solution extravasation.

Side effects from hyaluronidase use are rare and generally of the urticarial type. Because of its limited stability, it should be reconstituted with 0.9% sodium chloride solution immediately before use. The ideal concentration and quantity to inject after extravasation have been reported to be 75 units in a volume of 3 ml. Higher doses did not appear to improve clinical outcome after intradermal infiltration of 0.25 ml of 23.4% HS.36 For maximum effectiveness we recommend injecting the diluted solution into multiple sites around the extravasated area. Studies have demonstrated that hyaluronidase solution must be injected within 60 minutes of extravasation to be effective.37

Treatment

Whatever the cause of the ulceration, it must be dealt with when it occurs. Fortunately, ulcerations, when they do occur, are usually fairly small, averaging 4 mm in diameter in our practice. At this size primary healing usually leaves an acceptable scar (see Figure 15.9). In addition to various topical therapies directly applied to the ulcer, elevation of the affected extremity and systemic pentoxifylline may be helpful in minimizing the ulcer size.

Pentoxifylline may decrease tissue injury of ischemia-reperfusion by inhibiting the production of platelet-activating factor during reperfusion.38 Pentoxifylline should improve microcirculatory dysfunction observed during reperfusion of ischemic tissues. Pentoxifylline causes increased deformability of RBCs and lowers blood viscosity.39 The optimal dosage appears to be 25 mg/kg for protective effects in experimental studies in the canine gracilis muscle model. However, the dosage that produces maximal protective effects in humans is unknown.

We have found that the use of occlusive or hydrocolloid dressings results in an apparent decrease in wound healing time. Occlusive dressings do not speed healing of full-thickness ulcers until granulation tissue has formed. Hydrocolloid gel dressings enhance debridement of wounds, possibly through their pectin-gelatin base. Nongelatin, nonpectin hydrocolloid dressings only act to stimulate fibrin lysis. Thus its enhanced efficacy may be related to wound debride-ment, which always should be used either medically or surgically to promote granulation tissue formation. More important, the use of occlusive dressings decreases the pain associated with an open ulcer. Dressings must be changed every three to four days, and necrotic tissue should be sharply debrided every week or two as needed to promote granulation tissue. However, because an ulcer may take four to six weeks to heal completely even under ideal conditions, if possible, excision and closure of these lesions are recommended at the earliest possible time. This affords the patient the fastest healing and an acceptable scar.

How To Reduce Acne Scarring

How To Reduce Acne Scarring

Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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