complications of cutaneous cryosurgery

Volume 8 Number 4 April, 1983

Kasabach-Merritt syndrome

28. Zarem HA, Edgerton MT: Induced resolution of cavernous hemangiomas following prednisolone therapy, Plast Reconstructr Surg 39:76-83, 1967.

29. Harker LA, Slichter S J: Platelet and fibrinogen con- sumption in man. N Engl J Med 287:999-1005, 1972.

30. Hillman RS, Phillips LL: Clotting-fibrinolysis in a cavernous hemangioma. Am J Dis Child 113:649-653, 1967.

31. Didisheim P, Fuster V: Actions and clinical status of platelet-suppressive agents. Semin Hematol 15:55-72, 1978.

32. Koeh-Weser J, Weiss I-IJ: Antiplatelet therapy. N Engl J Med 298:1344-I347, 1978.

33. DeKlerk DJt, Northover RC: Giant hemangiomas of the scalp. A report of 2 cases. S Afr Med J 55:59-62, 1979.

34. Inglefield JT Jr, Tisdale PD, Fairchild JP: A case of hemangioma with thrombocytopenia in the newborn in- fant treated by total excision. J Pediatr 59:238-241, 1961.

Complications Richard F. Elton, M.D. Detroit, MI

of cutaneous cryosurgery

The complications of cutaneous cryosurgery may be divided into technical problems, those involving patient selection, reactions of the immediate and acute type, short-term reactions, and long-term complications. Technical problems involve primarily the delivery system and temperature monitoring. Proper patient selection is essential for avoiding complications. Reactions to cryotherapy vary widely from those which may be considered normal to hemorrhage, severe systemic reactions in cold-sensitive individuals, full-thickness skin necrosis, syncope, and sudden death. Short-term complications include hemorrhage, infection, and granuloma pyogenicum. Long-term reactions include pseudoepitheliomatous hyperplasia, nerve damage, pigmentary problems, tissue defects, delayed healing, scar formation, and the recurrence of benign and malignant lesions. (J AM ACAD DERMATOL 8:513-519, 1983.)

A place for cryosurgery has been firmly estab- lished in the armamentarium of many physicians, and for many dermatologists it may be the treatment of choice for a variety of benign and malignant skin lesions. Not only must the cryotherapist know which lesions to treat or not treat but also he must know the consequences of such treatment. In

From Wayne State University Department of Dermatology. Accepted for publication Aug. 26, 1982. Reprint requests to: Dr. Richard F. Elton, 22250 Providence Dr.,

Suite 301, Southfield, MI 48075.

competent hands, cryosurgery and, more specifi- cally, liquid nitrogen (LN2) therapy, has proved to be a safe and effective therapy. There are, how- ever, a number of possible complications with which the cryotherapist should be familiar? This work will review the known problems and will discuss other problems which are theoretically possible.

The complications of cryosurgery can, for practical purposes, be divided into technical problems, those involving patient selection, reactions of the immediate and acute type, short-term reactions, and long-term complications.

513

514 Elton

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Fig. 1. Positive ice cube test for cold urticaria. Such patients should not be treated cryosurgically.

Technical problems

Improvement in the past few years with liquid nitrogen spray delivery systems has reduced the incidence of unit clogging secondary to ice formation. This can still be a problem when the unit is run continuously or when used in a humid envi- ronment. Clogging can be kept to a minimum by not running the unit continuously and by being sure all parts are dry before filling with LN2.

In the treatment of skin cancer, it is desirous to reach temperatures of - 5 0 ~ to - 6 0 ~ C. Defective thermocouple needles or an inaccurately calibrated pyrometer may be a problem. Thermocouple needles should be periodically checked by inserting the needle tip into LN2 ( - 196 ~ C) and holding the needle tip in one's fingers ( - 3 7 ~ C). Ther- mocouple needles may be easily damaged with rough use and should be handled carefully.

LN2 runoff onto normal skin may occur when spray is directed at one spot without interruption and it also occurs with cotton-tipped applicators. This will cause a burn in unwanted areas, and one must be especially cautious to avoid runoff into the eyes. Treating forehead lesions in a sitting patient makes this more likely. Drapes, tape, or other material used to surround a lesion may allow LN2 to accumulate at its borders or underneath, causing "cryo" injury which may go unnoticed until after completion of the procedure.

The spattering of Iiquid nitrogen spray may lead to the appearance of multiple small erythematous macular lesions surrounding the treated area. This

Fig. 2. Nitrogen gas insufflation of the periorbital area after liquid nitrogen spray to an ulcerated BCE.

can be a cause of consternation to patient and physician unless the operator is aware of this phenomenon and seeks to prevent it.

i f used for long periods, around the nose and mouth, hypoxia secondary to breathing of LN2 may also occur. This may be avoided by using a closed probe or disc.

Problems involving patient selection

Many complications can be minimized or elim- inated with proper patient selection. Experienced cryosurgeons are well aware of the advantage of cryosurgery when treating multiple lesions, aged nursing home patients, those allergic to local anes- thesia, patients with pacemakers in whom elec- trocautery may be contraindicated, those on co- agulants, and patients who may have transmissible conditions such as serum hepatitis.

On the other hand, it is just as important to know what and who not to treat. Blacks and others with heavily pigmented skin are more likely to develop permanent hypopigmentation and depigmentation, and hence cryosurgery must be used with caution in these individuals. Patients with sensory loss should be treated with caution, as should those with areas having a poor blood sup- ply, such as the legs of many elderly patients.

Infants, the elderly, patients with sun-damaged skin, skin treated with long-term steroids, and


Complications of cryosurgery 515

those with irradiated skin will all react more vig- orously than those with normal adult skin. Those with other skin diseases, such as blistering disorders, should be treated with caution. In contrast to treating malignant lesions, one should always error on the conservative side in treating benign lesions. If necessary, treatment may be repeated.

Medical history is very important to rule out possible severe adverse reactions in cold-sensitive individuals. Cryoglobulinemia, cryofibrinogenemia, Raynaud's disease, and cold urticaria should be considered contraindications to cryosurgery. Caution should also be used in persons suspected of having a collagen vascular disease. Patients suspected of having any of these disorders should be screened with appropriate laboratory tests, including cryoglobulin and cryofibrinogen levels, the ice cube test for cold urticaria and an antinuclear antibody test (Fig. 1).

Reactions of immediate and acute type

Many of the immediate and acute reactions to LN2 therapy may be considered "normal ," but when occurring in an unsuspecting or exaggerated form may alarm both the physician and the patient. Most importantly, one should always fore- warn the patient of these possibilities.

Most procedures have a short minimal type of burning pain upon freezing and a somewhat more intense pain upon thawing. The pain of freezing is of short duration because of the self-anesthetizing feature of the freeze. In general, the deeper the freeze, the more intense the pain. Pain generally subsides within minutes after the thaw. Consider- able pain may occur when freezing the plantar surface, paronychial areas, the ear (especially near the canal), eyelids, lips, and mucous membranes. The local infiltration of lidocaine may be required before freezing lesions such as large warts on the plantar surface and paronychial areas. Deeper freezing on the forehead and temples may produce a migraine or vascular type of pain lasting for hours.

Urtication and edema occur within minutes of freezing and exudation within 12 to 24 hours. This is especially true with more extensive freezing. Exaggerated edema frequently occurs in the periorbital, forehead, and anterior scalp areas. Freez-

ing of the mid forehead may produce severe bilat- eral periorbital edema which may become depen- dent over the next few days. Severe edema occurs more often in infants and the elderly. Inner canthus freezing may produce temporary tearing secondary to severe periorbital swelling, with compression of the lacrimal duct. Cool compresses may help al- leviate some edema but antihistamines do not. Sys- temic steroids are only rarely indicated.

Hemorrhage occurring after LN2 therapy is rare but may occur when a biopsy is taken just prior to therapy and adequate hemostasis has not been se- cured. It may also occur after deep curettage and freezing in the treatment of skin cancers.

A very rare complication is nitrogen gas insufflation of subcutaneous tissue, which occurs only with the spray method of therapy. This occurs when gas enters the open path between the surface and subcutaneous tissue and can occur when spraying into a biopsy site. Clinically, one sees immediate bulging around the wound, especially in the periorbital area (Fig. 2). Pressure rings or cones will help prevent this when spraying open wounds.

The systemic effects of reactions in cold- sensitive individuals have been mentioned. Cryo- globulinemia, cryofibrinogenemia, cold urticaria, and Raynaud's disease are contraindications of cryosurgery. Collagen vascular disease is also in most instances a contraindication. A severe and prolonged reaction to LN2 application for a small wart on the leg was reported in a patient with cold urticaria. The possibility of inducing histamine shock in such individuals must be considered. 2 Deep full-thickness cutaneous necrosis of the face was reported to have occurred in a patient treated for ache scarring with LN2 spray. There was subsequent discovery of cryofibrinogenemia and a connective tissue disorder in this patient, a The tak- ing of a careful medical history will help to prevent these serious complications. I have seen and others have reported syncopal episodes occurring in patients receiving LN2 therapy for warts. 4 This is likely secondary to a vasovagal reaction. I and others have also reported febrile systemic toxic reactions occurring following cryosurgery, but this complication is very rare. 5 A more chilling reaction was cardiac arrest occurring in a per-

516 Elton

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Fig. 3. Postoperative Pseudomonas infection in a renal dialysis patient treated for a superficial BCE.

son treated for actinic keratoses of the lips and forehead with cotton-tipped LN2 applicators.6

Shor t - te rm reactions

Hemorrhage is unusual in postoperative cryosurgical wounds but can occur after deeper freezes where a tumor invades a vessel wall and "un- plugging" of the vessel occurs. This is more likely to be seen in areas such as the temples or behind the ear where larger vessels may be more superficial. Bleeding may also occur secondary to trauma of a healing cryosurgical wound where a deep crust is disrupted. One should always obtain hemostasis before freezing and instruct the patient in the use of pressure.

Postoperative infections are uncommon but may be seen in slow-healing wounds with a thick crust. Use of hydrogen peroxide, debridement, and topical antibiotics may be helpful. Infection should not be confused with necrotic tissue, which ap- pears like a light yellowish material stuck on the surface of the wound and is often seen after the deep freeze of a tumor. Prophylactic systemic antibiotics are rarely indicated except in wounds already infected or in those patients with an im- paired immune system. A postoperative Pseu- domonas infection developed in a renal dialysis patient treated by me for a superficial basal cell epithelioma (BCE) of the back (Fig. 3).

Granuloma pyogenicum has also been reported

Fig. 4. Pseudoepitheliomatous hyperplasla m a cryosurgical wound 4 weeks postoperatively.

to occur in a healing cryosurgical wound. 7 I have seen this secondary to treatment of an actinic keratosis on the face. It may be easily destroyed by electrodesiccation and curettage.

Long-term complications

A longer-term complication of the postoperative cryosurgical wound is pseudoepitheliomatous hyperplasia, which may begin in the first postoperative month and can be confused with a recurrence by one unfamiliar with its appearance. This is a self-limited complication and more often follows a deeper freeze. A biopsy may be performed if one is in doubt of the diagnosis (Fig. 4). Milia formation is more commonly seen after a deeper freeze, and these may be removed if they are cosmetically troublesome.

The most serious long-term complication of cryosurgery is nerve damage. Nerve tissue is sensitive to freezing damage, but the sheath is resis- tant. One must use special care in treating areas in which nerves lie superficially, and these include the sides of the fingers, angle of the jaw, postauricular area, the sides of the tongue, and the ulnar fossa of the elbow. Damage to nerves in several of these areas has been reported. 8-Z~

Votume 8 Number 4 April, 1983

Millns et al it reported three cases of nerve damage on the sides of the fingers. They felt that particu- larly vulnerable areas were the sensory nerves of the hand, common peroneal nerve as it overlies the fibular head, ulnar nerve at the medial epicondyle of the humerus, branches of the peroneal nerve to the dorsum of the foot, and the supra- and in- fraorbital nerves of the face. Anesthesias or pares- thesias of these areas are usually temporary but may last for many months. It is important to note that even though cutaneous cryosurgery is widely used, few cases of nerve damage have been reported and all appear to have been temporary. Bal- looning of tissue over vulnerable areas is helpful in preventing this complication (Fig. 5). This can be done by manually squeezing the tissue together over the vulnerable area or by injecting lidocaine under the lesion to be frozen.

Pigmentary problems following cryosurgery occur much more commonly in blacks and other deeply pigmented individuals. While localized temporary depigmentation is normal, permanent depigrnentation may occur with a deep freeze. Postinflammatory halo hyperpigmentation is frequent but self-limited. Repigmentation of a postoperative wound follows from the margin and adnexa. Cryosurgery should be used with caution in dark-skinned patients, and the patient should be forewarned.

Tissue defects occur most commonly when treating skin cancer. While atrophy can be ex- pected when the skin is involved with cancer, it may also follow the overtreatment of benign lesions. Cartilage defects occur only when the tumor has invaded the cartilage, giving cryosurgery a distinct advantage over other modes of treatment in these areas. Permanent crusting in the nose can occur secondary to mucous membrane atrophy when deep cryosurgery has been used in this area. Permanent alopecia may also occur after a deep freeze, lz Special regional tissue defects and complications, such as ectropion secondary to treatment of eyelid tumors, may occur. Ectropion formation is uncommon but is more likely to occur when the tumor is near the free margin of the eyelid. Notching of the eyelid and loss of eyelashes may occur when the tumor involves the

Complications of ct2cosurgepy 517

Fig. 5. Ballooning of skin over side of finger will help to preveat postcryosurgical nerve injury.

free margin of the lid. The absence of frequent complications involving the lids makes cryosurgery a very useful tool in dealing with tumors of this area. Wingfield and Fraunfelder 13 and Wood and Anderson ~4 reviewed possible complications secondary to cryotherapy in this area. The permanent upward notching of the upper lip may occur when tumors are frozen on or near the ver- milion border. I have experienced this on one occasion, and Zacarian* has seen this not infre- quently. Tumors of this area are best treated by means other than cryosurgery.

Delayed healing of cryosurgical wounds may result in hypertrophic scar formation. Hypertro- phic scar formation is uncommon but has been reported following the combination of LN2 and topical tretinoin at the site of a treated BCE. t~ Hypertrophic scars may be easily treated with the use of intralesional steroids. Ulceration may occur with delayed healing. A patient developed marked periorbital edema several hours following a 10- to 15-second freeze. An emergency room physician suspected angioedema and administered intrave- nous steroids and epinephrine. An area of delayed healing developed, resulting in deep scarring at the treatment site. It was postulated that steroids plus epinephrine may have contributed to delayed

*Zacarian SA: Personal conununication.

518 Elton Journal of the

American Academy of Dermatology

Fig. 6. Recurrent BCE at a postcryosurgical site. Note recurrence at margin.

healing. Graham,* in personal communication with the physician involved in this case, believes that manipulation of the treatment eschar may have contributed to the scarring. In general, unless there is evidence of infection, it is best not to manipulate or remove the original treatment eschar. Grahamt also stressed the need for caution in treating patients with hyperelastic skin as these tend to form atrophic scars more easily. Graham 1~ also reported hypertrophic scar formation in three patients with severe acne conglobata treated with LN2. An ulcer developed beyond the treated area on the leg of a patient with a seborrheic keratosis treated with an LN2 swab. Fisher 17 felt that cryosurgery on the legs was ill advised. In my experience, with the proper selection of patients, cryosurgery is a safe and effective treatment for lesions on the legs. Patients with compromised circulation, the elderly with stasis problems, and diabetics tend to heal poorly after cryosurgery, and it is best avoided in these patients. Malignant lesions on the legs which are frozen deeply may be very slow to heal.

One should always give the patient a realistic idea of the possible end results concerning tissue

*Graham GF: Personal communication.

defects, and especially so when treating skin cancer. A patient is more likely to accept defects secondary to treating skin cancer than when benign lesions are treated.

Recurrence of benign lesions and skin cancers

It is always best to error on the side of under- freezing when treating benign lesions. One can always retreat if necessary. One phenomenon that occurs with the cryosurgical treatment of warts is recurrence around the periphery of the area treated. This is not uncommon with this modality. With the proper selection of patients and with the careful monitoring of temperature, cure rates involving the cryosurgical treatment of skin cancer are very high. When recurrences appear, they are most likely to be seen at the margins of the lesion rather than the center (Fig. 6). Larger lesions, i.e., those greater than 2 cm, may also recur at the center and are more disturbing in that the postoperative scar may appear normal with tumor located under the scar. In my experience, this is especially true in cases of deep, penetrating malignant neo- plasms and in sclerosing basal cell epitheliomas. In those cases in which one is suspicious of a possible recurrence, a subsequent biopsy 3 to 6 months after cryosurgery is advisable. '8 Again, patient selection is very important, and alternate therapy may be indicated.

Sako 19 showed a 20% recurrence rate in sixty patients with leukoplakia treated cryosurgically with a 2'/2- to 4-year follow-up. There was a 6.6% malignant transformation in this period. Zaca- rian z~ recently reported a 10% recurrence rate in the treatment of lentigo maligna with LN2 therapy.

A more disturbing report was that of Pospisil and MacDonald, 21 who showed that in premalig- nant lesions of hamster cheek pouch, partial treatment by cryosurgery was shown to potentiate subsequent tumor development. Pospisil and Mac- Donald 19 had earlier theorized that although cryosurgery gives satisfactory results initially, it is possible that it may render the adjacent tissue sus- ceptible to the development of further lesions or to malignant transformation. Thus far this theory cannot be supported from the general clinical evidence available to us from the treatment of thou- sands of patients in this country.


Complications of cryosurgery

Complications of cutaneous cryosurgery are not common, and some problems arise because of the lack of skill and experience of the physician who uses cryosurgery. With the proper selection of patients and with adequate training in the use of this modality, cryosurgery is a most effective thera- peutic tool in the treatment of many cutaneous lesions.

REFERENCES

1. McMeekin TO, Moschella SL: Iatrogenic complications of dermatologic therapy. Med Clin North Am 63:441- 453, 1979.

2. Hoke AW: A chilling thought. Arch Dermatol 112:122, 1976. (Letter to Editor.)

3. Stewart RG, Graham GF: A complication of cryosurgery in a patient with cryofibrinogenemia. J Dermatol Surg Oncol 4:743-744, 1978.

4. Epstein AM, Shapock JL: Syncope associated with liquid nitrogen therapy. Arch Dermatol 113:847, 1977. (Letter to Editor.)

5. Elton RF: Personal communication, in Zacarian SA: Cryosurgical advances in dermatology and tumors of the head and neck. Springfield, IL, 1977, Charles C Thomas, Publisher, p. 138.

6. Goldstein N: Cardiac arrest following application of liquid nitrogen. J Dermatol Surg Oncol 5:602, 1979.

7. Greer KE, Bishop GE: Pyogenic granuloma as a complication of cryosurgery. Arch Dermatol 111:1536-1537, 1975.

8. Gage AA: Deep cryosurgery, in Epstein E: Skin surgery. Springfield, IL, i970, Charles C Thomas, Publisher, pp. 648-671.

9. Nix "rE: Liquid nitrogen neuropathy. Arch Dermatol 92:185-187, 1965.

10. Finelli PF: Ulnar neuropathy after liquid nitrogen cryotherapy. Arch Dermatol 111:1340-1342, 1975.

11. Millns JL, et al: Neurological complications of cryosurgery. J Dermatol Surg Oncol 6:207-213, 1980.

12. Elton RF: The course of events following cryosurgery. J Dermatol Surg Oncol 3:448-451, 1977.

13. Wingfield DL, Fraunfelder FT: Possible complications secondary to cryotherapy. Ophthalmic Surg 10:47-55, 1979.

14. Wood JR, Anderson RL: Complications of cryosurgery. Arch Ophthalmol 99:460-463, 1981.

15. Peck GL: Hypertrophic scar after cryotherapy and topical tretinoin. Arch Dermatol 108:819-822, 1973.

16. Graham GF: Cryotherapy in the treatment of acne, in Epstein E: Skin surgery. Springfield, IL, 1977, Charles C Thomas, PuNisher, pp. 681-697.

17. Fisher DA: Capital letter. Cold feet. J Dermatol Surg Oncol 4:552-553, 1978.

18. Elton RF: Wisdom of subsequent biopsies. J Dermatol Surg Oncol 3:286, 1977.

19. Sako K, et al: Cryotherapy for intraoral leukoplakia. Am J Surg 124:482-484, 1972.

20. Zacarian SA: Cryosargical treatment of lentigo maligna, Arch Dermatol 118:89-92, 1982.

21. Pospisil OA, MacDonald DG: The tumor potentiating effect of cryosurgery on carcinogen treated hamster cheek pouch. Br J Oral Surg 19:96-104, 1981.

'[I ~ i I

Diagnosis of spongiotic vesicular dermatitis by Tzanck smear: The "tadpole cell" Robert J. Pariser, M.D. Norfolk, VA

Cells with a "tadpole-like" shape were found in 8.3% of Tzanck smears from patients with spongiotic vesicular dermatitis. A variety of other vesicobullous disorders did not show these cells. The presence of such cells is a reliable, readily available marker of diseases having spongiotic blisters. (J AM ACAD D~RMATOL 8:519-522, 1983.)

From the Departments of Medicine (Dermatology) and Pathology, Eastern Virginia Medical School.

Accepted for publication Aug. 26, 1982. No reprints available.

The Tzanck smear (cytopathologic smear of the walls and contents of a blister) is a useful technic for diagnosis o f several vesicular or bullous disorders of the skin, notably herpes infections and

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complications of cutaneous cryosurgery

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