Transplantation of Actinically Damaged Skin

TRANSPLANTATION OF ACTINICALLY DAMAGED SKIN* WILLIAM GERSTEIN, M.D. AND ROBERT G. FREEMAN, M.D. The aging skin has been under intense scrutiny in recent years. A variety of changes have been described clinically and histologically. The dry, leathery, wrinkled, weather-beaten skin of the farmer and sailor is familiar to all. This is associated with basophilic degeneration in the upper dermis and the appearance of fibers having the staining and amino acid composition characteristic of elastic tissue.(1)

Restriction of these alterations to only the exposed parts of the body has incriminated sunlight as the principal evocative agent. Ultraviolet effects on the skin arc cumulative and a correlation exists between the total exposure to sunlight and the degree of damage (2, 3). The importance of these findings is emphasized by the repeated

Exchange autografts were performed between exposed and unexposed skin. The sites selected

were the posterior aspect of the neck and the

medial brachial area. This latter site showed no clinical or histologic evidence of actinically-induced changes in any of the volunteers. In 14 instances the graft from the neck was exchanged with that from the arm, while in the remaining 4

individuals the free graft was replaced in its

original site to serve as a control. Specimens for histologic examination were obtained from each site. The skin was cleansed with alcohol and Xylocaine® 1 per cent was injected locally. Grafts were

obtained with an 8 mm punch through the depth of the dermis from each site. Grafts were retained

in place by passing two 5-0 black silk sutures through the walls of the receiving site and over the graft without penetrating it. A dry gauze dressing was placed over the area and all sutures

observations that skin cancer occurs predomi- were removed after one week. nantly on exposed sites among individuals who The grafts were observed at regular intervals live in latitudes with great amounts of sunshine and then excised at the end of the observation (4). The production of cutaneous carcinomas by period. Tissue was fixed in 10 per cent formalin sections stained with hematoxylin and eosin, ultraviolet irradiation in animals is laboratory and as well as stains for elastic tissue, collagen and confirmation of the clinical findings (5). Reduc- mucopolysaccharides. Evaluation of dermal changes was based on tion in the number of such experimental tumors by means of topical sunscreens is an intriguing routine hematoxylin and eosin sections as well as observation.6 To assess the effect of the biological milieu on the permanence of actinic change, full-thickness

trichrome stains for collagen and Gomori's aIdehyde fucbsin, orcein Giemsa and Vcrhoff's elastic tissue stains for elastic tissue and Wilder's technic

for reticulin. The composite evaluation of the

skin grafts from exposed areas of the body degree of damage was estimated on a scale from showing clinical evidence of sun-induced damage were exchanged with grafts from sites not usually exposed to sunlight. These grafts were left in situ for several months, observed at regular intervals

and then excised for histologic examination.

0 to 4+. This evaluation was made independently

without knowing the method of grafting used. The evaluation was made on the basis of the amount of orcein-Gicmsa and aldchyde fuchsin positive connective tissue present and on the staining qualities of collagen as observed in triebrome and hematoxylin and eosin sections.

METHODS AND MATERIALS

Volunteers for the study, inmates of the Huntsville unit of the Texas Department of Corrections,

GROSS OBSERvATIONS

included 15 white and 3 Latin-American men

Grafts were uniformly successful except in two

between 41 and 72 years of age. Their skin showed

instances when loss occurred during the first

varying degrees of change attributable to chronic

exposure to sunlight. A correlation existed between the age of the individuals and the amount of clinically evident damage to the exposed skin, the younger men having less degeneration. * From

the Department of Dermatology, Baylor University College of Medicine and Veterans Administration Hospital, Houston,

week because of mechanical reasons.

Arm Skin to Neck: After the initial period of inflammation which accompanies healing, the morphologic appearance of arm skin was retained. The grafts were lighter than the adjacent skin and

Texas.

Presented at the Twenty-fourth Annual Meet-

ing of The Society for Investigative Dermatology, Inc., Atlantic City, N. J., June 20, 1963. 445

pigmentation did not increase noticeably. Some grafts maintained a minimal crythema. In most instances the surface of these grafts was depressed below the surrounding host skin and in none did

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Fin. 1. The skin of the neck of one of the vol-

unteers shows wrinkling nnd actinic degeneration. A graft of skin from the arm appears unchanged after nine months.

actinic changes develop during the ten months' observation period. Neck Skin to Arm: After the initial period of healing, i.e. two to three weeks, the grafts remained in striking contrast to the surrounding

FIG. 2. Skin from the neck of the person shown in Fig. 1 was transplanted to the inner surface of the arm and it retained the characteristics of degenerated skin, both clinically and microscopically.

Fin. 3. The most frequent change seen in transplants of neck skin placed on the arm was central

clearing as illustrated by this eight month old skin of the arm. They were slightly elevated graft. above the adjacent skin surface and brown pigmentation persisted, some showing a yellow hue became depressed below the level of the surroundin the deeper portion. Several of the transplants ing skin.

Arm Skin to Arm (Control): Here, too, the retained one or more actively growing hairs. graft retained its morphologic identity, not After several months the grafts flattened to the differing from the surrounding skin at the end same level as the surrounding skin. A loss of pigmentation in the center of some grafts yielded

a resemblance to adjacent skin. The periphery of these grafts, however, remained pigmented and clearly distinct from their surroundings. None of these reverted to an appearance entirely

resembling normal skin during the period of observation. Neck Skin to Neck (Control): These grafts retained the morphologic identity of neck skin and

were often difficult to distinguish. They never

the end of the observation period.

icnoscopic oBsERVATIONs

Epidermis. The epidermis of actinically de-

generated skin was thin and there was effacement of rcte ridges. Prickle cells were irregular in dis-

tribution and maturation. The extent of these epidermal changes correlated with the extent of dermal connective tissue degeneration. In each instance skin from the arm showed no such change

and none developed in transplants placed in exposed areas for as long as 9j months. When ac-

TRANSPLANTATION OF ACTINICALLY DAMAGED SKIN

447

tinically degenerated skin from the neck was No change was observed when exposed skin moved to the arm, one graft showed slight re- from the neck was replaced in the original site. gression and ten showed definite regression with Elastic tissue stains consistently showed more thickening of the epidermis, reappearance of rete degenerative "elastotic" connective tissue than ridges and restoration of more uniform maturation of epidermal cells. There was no significant change in the grafted epidermis in three patients nor in the control grafts. (Table 1) Dermis. In every case it was readily apparent which grafts had been left in place and which had been changed from exposed to unexposed areas. Eleven of 14 grafts changed to unexposed areas

was apparent from trichrome or hematoxylin and eosin stains. Degenerated collagen was amorphous and grey on tricbrome stained preparations; disappearance of this material with replacement by

showed definite improvement. (Table 2). Only one

normal papillary dermis was present. In grafts changed to unexposed areas this grenz zone be-

of these showed complete regression and in this case degenerative changes in the initial biopsy were minimal. Seven of the remaining ten grafts had a decreased amount of actinic degeneration

of connective tissue. This was distinctly more evident with almost complete regression at the

brilliant green normal-appearing collagen was construed as evidence of regression. With severe

collagen degeneration in the original biopsy specimens from the neck a narrow grenz zone of came wider as regression of actinic degeneration

occurred. This widening also usually accompanied an improved appearance of the epidermis. COMMENT

center of the graft and less at the margins.

Various observations indicate that certain damaging effects of sunlight on the skin can be inhibited or reversed. For example, the number of epitheliomas decreases after administration

TABLE 1 Restoration of Epidermis in Grafts Moderate Slight No Change Restoration Restoration Totals

Groups

Control

—

4 3

Test

1

—

4

10

14

TABLE 2 Change in Dermat Connective Tissue Degeneration Groups

Control

Test

ModerNo Slightly Im- Complete Totals Change Improved ately proved Regression

4 3

—

—

—

5

5

1

4 14

of chloroquine.(7) Formisano, Kligman and Montagna described restoration of epidermal changes following topical application of hormone

creams(S) The common practice of using a topical cream or ointment for patients with skin cancers and precancerous lesions appears to decrease the number of such lesions. Increase in number of skin cancers during tbe summer suggests that the development of cancerous and precancerous skin lesions correlated with recent exposure to sunlight in addition to longterm cumulative exposure. Actinic damage to exposed skin must be at least partially reversible and our findings support the concept that pro-

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Fsa. 4. The central clearing was also evident microscopically. Elastotic fibers remain only at the periphery as black aggregates. (Gomori's aldehyde fuchsin; Mag. 23 X)

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FIG. 5. Actinic degeneration of collagen and elastosis are evident in this biopsy taken from the skin of the neck at the time of transplantation. (H & E stain; 198 X) FIG. 6. Skin from the neck was transplanted to the arm and nine and one-half months later the graft was excised. The areas of actinic degeneration were largely replaced by normal appearing collagen and in other stains restoration of a normal elastic tissue pattern was also observed. (H & E stain; 198 X) 448

TRANSPLANTATION OF ACTINICALLY DAMAGED SKIN

tection from continued exposure promotes some regression even in severe aetinic degeneration of skin. No such improvement occurred in control

449

unexposed areas of the upper arm. After observa-

tions for as long as 9} months, regression of aetinie degeneration occurred in the epidermis

grafts left in exposed sites. The influence of a and in dermal connective tissue. No improvement new donor site environment as the only cause was seen in 4 control grafts left in exposed areas. When previously unexposed skin was moved to for regression seems unlikely. The interesting and unexpected occurrence an exposed area, actinic degeneration did not of more clearing in the center of the graft than appear. at the margins is unexplained. Possibly this REFERENCES relates to revaseularization of the grafted skin. 1. SMITH, J. GRAHAM, Jx., DAvIDsoN, E. A., The dermal changes associated with abrasion SAMS, W. M., Ja. AND CLARK, R. D.: Alreported by Ayres, Wilson and Luikart followed

actual removal of much of the degenerated tissue and thus are not directly analagous to the present study.(9) The presence of hairs in the transplant demon-

strate conclusively the success of these fullthickness grafts. One failure was recognized grossly and microscopically.

Interestingly, actinic degeneration did not

terations in human dermal connective tissue with age and chronic sun damage.

J. Invest. Derm., 39: 347, 1962. 2. KNOX, J. M., COCKHRRLL, E. G. AND Faza-

MAN, R. G.: Etiological factors and premature aging. J. A. M. A., 179: 630, 1962.

3. SMITH, J. GRAHAM, Ja. AND LANSING, A. I.:

The distribution of solar elastosis (senile elastosis) in the skin. J. Geront., 14: 496, 1959.

4. MCDONALD, E. C.: The epidemiology of skin cancer. J. Invest. Derm., 32: 379, 1959.

develop in arm skin placed on an exposed area of the neck. Perhaps studies of greater duration will will enable us to determine the time required to produce such changes. One graft is still in place and additional grafts are planned. As dermal changes have been considered to be the forerunner of epidermal carcinomas (10), the

5. BaUM, H. F.: Carcinogenesis by Ultraviolet

improvement in the actinic degeneration of the dermis suggests that available means of protecting skin against sunlight exposure might help to delay aging of exposed skin and reduce the incidence of precancerous and cancerous lesions.

TAGNA, W.: Effects of topically applied steroids on exposed aged skin. Presented at 23rd Annual Meeting Society for Investigative Dermatology, Chicago, 1962.

SUMMARY

In 14 patients full-thickness skin grafts were exchanged between exposed areas of the neck and

Light. Princeton, N. J., Princeton University Press, 1959.

6. KNOX, J. M., GRIFFIN, A. C. AND RAKIM, R.

E.: Protection from ultraviolet carcinogenesis. J. Invest. Derm., 34: 51, 1960.

7. KNOX, J. M. AND FRERMAN, H. C.: Prophylac-

tic use of chloroquine to prevent skin cancer. Arch. Derm. (Chicago), 87: 315, 1963. S. Foaans.&rco, V., KLIGHAN, A. M. AND M0N-

9. Avaxs, S., III, WILsoN, J. W. AND LUIKART,

H., II.: Dermal changes following abrasion. Arch. Derm. (Chicago), 79: 553, 1959. 10. MACaIR, B. S. AND MCGOvERN, V. J.: The mechanism of solar carcinogenesis. Arch. Derm. (Chicago), 78: 218, 1958.

DISCUSSION DR. J. GRAHAM SMITH, Jn. (Durham, N. C.): This work, insofar as I know, is the first objective

study demonstrating, both clinically and histologically, that the changes of actinic elastosis may be reversible. Dr. Gerstein, would you speculate on the cen-

mal-dermal junction. I hope Dr. Gerstein will comment about this. DR. RICHARD L. DOBSON (Portland, Oregon):

I would like to join in congratulating the authors

on a very fine presentation. However, I would like to point out that we must differentiate betral clearing which was observed? I would have tween aging and actinic change. Several times expected peripheral clearing at the site of excision during the presentation, there was a confusion where there was fibroblastic activity with increased in terms; where aging was specified, I am sure synthesis of connective tissue associated with that actinie damage was meant. DR. RUDOLF L. BAER (New York, N.Y.): I wound healing. In one slide of a transplant of aetinieally ex- also enjoyed the presentation very much. I posed skin to normal skin, there was an increase would like to ask the authors whether they also

in normal-appearing collagen beneath the epider- carried out controls grafting areas of actinic

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skin into another area of actinic skin. This would is concerned, we have no good explanation for be a necessary control in order to rule out the this. Perhaps the work of Bullough on wound vascular and other effects of wound healing at hormone would apply here (Bullough, W. S. and the site of a skin graft.

Laurence, E. B.: The Control of Epidermal

I would also like to call the attention of the Mitotic Activity in the Mouse, Proc. Royal Soc. audience to an excellent way of preventing London, Ser. B 151 :517-536, 1960). actinic damage which is used by Moslem women, As to the appearance of the so called Grenz that is to always wear a veil when outdoors. zone, we saw this in only one instance and we Experts tell me that these women, who never are at a loss to explain it. expose their faces except for their eyes, have the best-looking skins, even at an old age.

Dr. Dobson is correct in pointing out that there

is, indeed, actinic change here and not aging.

This is elaborated upon in the the written paper. Dr. Baer, we did try to assess the influence of What does happen if you just shield from light wound healing in our controls by removing the an area of so-called actinically changed skin; aetinic skin and treating it the same way as we that is, shield it for a year? Has anyone done did the transplants, and then placing it back into anything like that? its original site. We did not, however, transfer DR. WILLIAM GERSTEIN (in closing): I wish it from one area to another. to thank the discussants for their kind remarks. Dr. Mescon, I do not know of any work on Dr. Smith, as far as the clearing in the center the controls you suggest. DR. HERBERT MESCON (Boston, Mass.): I am

not sure that I understood all your controls.

THE JOURNAL OF INVESTIGATIVE DERMATOLOGY

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