squamous cell carcinoma may be preferable to the alterna¬ tive of ineffective management of a recalcitrant, often dis¬ abling, benign condition for which grenz ray therapy is em¬
ployed. Our only patient with a known cutaneous malignancy re¬ lated to x-ray or grenz ray treatment is
a man
whose inca¬
pacitating histiocytosis X limited to the scalp was brought under complete control with grenz ray therapy over a 5-year period. The total dose in this instance was over 200 Gy, and a single small squamous cell carcinoma that resulted was easily removed. Surely he will develop other basal or squamous cell carcinomas, but the benefit-risk ratio for his disability seems obvious. The same argument applies in a less dramatic way with
conditions and much lower doses. We con¬ sider grenz ray therapy an integral part of the management of psoriasis of the scalp, Darier's disease, recalcitrant lichen simplex chronicus, lichen planus, pustulosis palmaris et plantaris, and other troublesome, but not life-threatening, conditions. In the doses employed the risks fall far below those associated with many other types of topical and sys¬ temic therapy currently in use. Our point is not to disagree with Burns' analysis but, rather, to emphasize to the reader that the benefits of su¬ perficial cutaneous radiation, properly given, far outweigh the potential risk. Any safe, effective, -economical form of therapy becomes extremely valuable in the practice of clin¬ ical medicine. Our patients should not be denied these valu¬ able tools. Frederick A. J. Kingery, MD Paul S. Russell, MD Walter G. Larsen, MD Portland Dermatology Clinic 2250 NW Flanders St Portland, OR 97210
1. Adriaans
1989;125:1005.
B, du Vivier A. Acne in
an
irradiated
area.
Arch
Dermatol.
2. Held JL, Bank DE, Grossman ME. Grover's disease induced by ionizing radiation. J Am Acad Dermatol. 1988;19:137-138.
In Reply.\p=m-\ We note the helpful letter from Held and Grossman. In our patients the diagnosis was made on the typical features of acne, namely comedones, papules, and pustules. We accept the fact that the patient described by Held and Grossman had a papular eruption with no other clinical features to suggest a specific diagnosis. A biopsy might thus have been essential there. While we accept that a biopsy may have added to the diagnosis in our patients,
more common
1. Burns FJ. Cancer risk associated with therapeutic irradiation of skin. Arch Dermatol. 1989;125:979-981. 2. Lindel\l=o"\fB, Eklund G. Incidence of malignant skin tumors in 14140 patients after grenz-ray treatment for benign skin disorders. Arch Dermatol.
Close-up
Beverley Adriaans, MD Anthony du Vivier, MD Dermatology Department King's College Hospital
3. Mortensen AC, Kjeldsen H. Carcinomas following grenz ray treatment of benign dermatoses. Acta Derm Venereol. 1987;67:523-525. an
Denmark Hill London SE5 9RS,
Irradiated Area
To the Editor.\p=m-\Adriaans and duVivier1 recently described two patients who developed papulopustular eruptions following radiation therapy for breast carcinoma. The authors conclude that radiotherapy may induce acne vulgaris at treated sites. Since acne vulgaris is known to respond to X-ray therapy (albeit with unacceptable sequelae), their ultimate claim appears questionable, particularly since neither patient's diagnosis was confirmed by biopsy. It seems entirely possible that both patients represent instances of Grover's disease (transient acantholytic dermatosis) induced by ionizing radiation. One such patient was recently described,2 with biopsy confirmation, following radiotherapy for lung carcinoma. Other entities such as eruptive vellus hair cysts and pityrosporum folliculitis may also mimic acne on the trunk. Once again, contributors to the dermatologic literature are encouraged to support their claims with biopsy confirmation. Fixed tissue will more easily withstand the rigors of future revisionism. Jonathan L. Held, MD Department of Dermatology Nashoba Community Hospital 190 Groton Rd
Ayer, MA 01432
patient's papular eruptions.
both our patients had an excellent response to therapy, and close-up views of the eruptions were submitted (Figure) that are very convincing, but we were limited by the number of pictures we were permitted to publish.
1986;122:1391-1395.
Acne in
view of
England
Dermatologic Radiation and Cancer To the Editor.\p=m-\The editorial in the July 1989 issue of the Archives requires a response. Burns1 confuses grenz ray therapy with superficial radiation, overestimates the cancer risk following grenz ray therapy, and thereby invites confusion.
A common mistake made by Burns in this editorial is grouping grenz ray with other x-ray modalities, and it is the
purpose of this letter to report the existing risk estimates and to clarify the confusion between grenz rays and superficial x-rays. Grenz ray is defined as that x-ray having a half-value
layer between 0.016 and 0.035 mm of aluminum, or a tube voltage of from 10 to 15 kV (50% of grenz rays are absorbed by 0.5 mm of skin).2 Burns1 states, "Nevertheless, several studies have established the carcinogenicity of skin radiation therapies by conducting long-term follow-up of patients exposed to ionizing radiation in the form of low-voltage x-rays or grenz rays." The data from the Swedish study by Lindel\l=o"\fand Eklund3
Downloaded From: http://archderm.jamanetwork.com/ by a New York University User on 05/22/2015
yields a risk for squamous cell cancer of 0.2 for 10 000 per¬
per gray, not 40 per 10 000 persons per gray as stated by Burns. A total of 14 237 patients received therapeutic grenz rays sons
for therapy of benign conditions. Average follow-up time is 15 years. In 58 patients, a malignant skin tumor was diag¬ nosed more than 5 years after grenz ray therapy. Nineteen patients had malignant melanomas, and 39 patients had other malignant skin tumors. The expected number of mel¬ anomas was 17.8, and that of other malignant skin tumors was 26.9. None of the patients with malignant melanomas, and only 8 of the patients with other skin tumors, had re¬ ceived grenz ray therapy at the site of the tumor. Six of the 8 patients with other skin tumors had been exposed to other known carcinogens. Four hundred eighty-one patients re¬ ceived accumulated doses of grenz rays greater than or equal to 100 Gy on one and the same area. No malignancies were found on these areas.3 Burns' states, "The incidence of basal cell carcinomas (BCC) was estimated to be 355 per 10" persons per gray (in a follow-up study of children irradiated for tinea capitis)." Note the modality discussed here is not grenz ray but su¬ perficial radiation having an average half-value layer of 0.9 mm of aluminum produced by 100 kV of unfiltered radiation through a glass tube. Burns1 states, "The thyroid gland is one of the more ra¬ diosensitive organs in the body, and thyroid adenomas are frequently seen after head or neck irradiation." Studies at the Skin and Cancer Unit of New York (NY) University Medical Center show that a maximum of 0.06 Gy administered to 2200 children who were irradiated for tinea capitis produced six thyroid adenomas; certainly not a fre¬ quent sequelae. Also, this treatment with superficial x-rays was abandoned in the 1950s. Goldschmidt et al2 have shown that the average thyroid dose per 1000 R to the side of the face with a half-value layer of 0.75 mm of aluminum, properly shielded, is an average of 0.002 Gy. Burns' states, "Skin cancer occurs frequently enough af¬ ter grenz ray treatment for lichen sclerosus of the vulva and psoriasis of the scalp that a dosage limit of 0.5 Gy/wk is recommended." This conclusion is unfounded, based on the very fine ar¬ ticle by Lindelöf and Eklund, misquoted by Burns; 4 Gy/wk was recommended for psoriasis of the scalp." Burns' states, "The high risk of BCC following irradiation of skin with grenz rays, x-rays, or PUVA makes it doubtful that the use of such therapies can be justified for benign conditions when other effective therapies are available." In their "Literature Review of Cutaneous Neoplasms Produced by Grenz Rays in Humans" (Table 2), Lindelöf and Eklund3 record only two BCCs.3 This certainly cannot be classified as a "high risk." In both of the above cases, the dose of grenz ray therapy received by the patient is unknown. Unfortunately, basal cell carcinoma was not reported in the Swedish study as this is not a registered lesion. How¬ ever, in a follow-up study of 3531 patients by Kopf5 treated with curettage-electrodesiccation, x-ray, and excision for basal cell carcinoma, the 5-year recurrence rate was 20%, 9%, and 9%, respectively. The x-ray therapy was, in this case, superficial x-rays (half-value layer, 0.9 mm alumi¬ num). Even in the case of treatment for basal cell carci¬ noma, a recurrence rate for basal cell carcinoma at the treatment site was smaller than or equal to that for the other modalities. In summary, grenz ray therapy has not been shown to be a significant carcinogenic risk. Radiation in the grenz ray
and
superficial x-ray peutic modality.
range remains
a
very useful thera¬
Arthur H. Gladstein, MD Skin and Cancer Unit Department of Dermatology New York University Medical Center 562 First Ave New York, NY 10016
1. Burns FJ. Cancer risk associated with therapeutic irradiation of skin. Arch Dermatol. 1989;125:979-981. 2. Goldschmidt H, Gorson RO, Lassen M. Dermatologic radiotherapy and thyroid cancer: dose measurements and risk quantification. Arch Dermatol.
1983;119:383-390. 3. Lindel\l=o"\fB, Eklund G. Incidence of malignant skin tumors in 14140 patients after grenz-ray treatment for benign skin disorders. Arch Dermatol. 1986;122:1391-1395. 4. Lindel\l=o"\fB, Lagerholm B, Liden S. Skin cancer caused by grenz rays. Acta Derm Venereol (Stockh). 1988;68:275-276. 5. Kopf AW. Computer analysis of 3531 basal cell carcinomas of the skin. J Dermatol. 1979;6:267-282.
More Questions About Purpura Fulminans
To the Editor.\p=m-\Ifound the report by Auletta and Headington1 on the relation between purpura fulminans and congenital or acquired severe protein C deficiency most illuminating in a realm that had been murky before. Several additional questions arise. First, what are the histopathologic findings of the early blanchable lesions, or of those skin lesions that resolve spontaneously, quickly, and without scarring? It would be hard to invoke significant
red blood cell extravasation with these features. Could there be a reactive dilatation of thrombus-free or at least unoccluded cutaneous arterioles and venules near those filled with fibrin thrombi? Is there significant cutaneous edema, perhaps from the same mechanism, in watershed zones that do not ultimately suffer intracutaneous and subcutaneous hemorrhage and cutaneous necrosis? Have biopsies ever been performed on early or nonprogressive lesions, either in human patients or in an animal model and, if so, what have they shown? Second, it is worth noting that effective outpatient therapy of protein C deficiency with warfarin does not affect ei¬ ther of those procoagulant factors ordinarily directly inac¬ tivated by protein C, namely, factors V and VIII. Rather, warfarin down-regulates synthesis of other, more suscepti¬ ble proteins. Finally, is it known why infants who are homozygous for protein C deficiency can have a delay in the appearance of purpura fulminans? One's first impression, that the mole¬ cule is too large for transplacental transmission, cannot be correct, since larger immunoglobulin molecules are well known to cross the placenta. Given a plasma half-life of only 8 hours for protein C, it seems remarkable that even with intrauterine transplacental "loading," any homozygousdeficient infant would not develop severe symptoms within the first 4 half-lives, let alone 15 as in the case described here! Henry Schneiderman, MD Room CG-058 University of Connecticut Health Center Farmington, CT 06032-9984 1. Auletta MJ, Headington JT. Purpura fulminans: a cutaneous manifestation of severe protein C deficiency. Arch Dermatol. 1988;124:1387\x=req-\ 1391.
Downloaded From: http://archderm.jamanetwork.com/ by a New York University User on 05/22/2015
ployed. Our only patient with a known cutaneous malignancy re¬ lated to x-ray or grenz ray treatment is
a man
whose inca¬
pacitating histiocytosis X limited to the scalp was brought under complete control with grenz ray therapy over a 5-year period. The total dose in this instance was over 200 Gy, and a single small squamous cell carcinoma that resulted was easily removed. Surely he will develop other basal or squamous cell carcinomas, but the benefit-risk ratio for his disability seems obvious. The same argument applies in a less dramatic way with
conditions and much lower doses. We con¬ sider grenz ray therapy an integral part of the management of psoriasis of the scalp, Darier's disease, recalcitrant lichen simplex chronicus, lichen planus, pustulosis palmaris et plantaris, and other troublesome, but not life-threatening, conditions. In the doses employed the risks fall far below those associated with many other types of topical and sys¬ temic therapy currently in use. Our point is not to disagree with Burns' analysis but, rather, to emphasize to the reader that the benefits of su¬ perficial cutaneous radiation, properly given, far outweigh the potential risk. Any safe, effective, -economical form of therapy becomes extremely valuable in the practice of clin¬ ical medicine. Our patients should not be denied these valu¬ able tools. Frederick A. J. Kingery, MD Paul S. Russell, MD Walter G. Larsen, MD Portland Dermatology Clinic 2250 NW Flanders St Portland, OR 97210
1. Adriaans
1989;125:1005.
B, du Vivier A. Acne in
an
irradiated
area.
Arch
Dermatol.
2. Held JL, Bank DE, Grossman ME. Grover's disease induced by ionizing radiation. J Am Acad Dermatol. 1988;19:137-138.
In Reply.\p=m-\ We note the helpful letter from Held and Grossman. In our patients the diagnosis was made on the typical features of acne, namely comedones, papules, and pustules. We accept the fact that the patient described by Held and Grossman had a papular eruption with no other clinical features to suggest a specific diagnosis. A biopsy might thus have been essential there. While we accept that a biopsy may have added to the diagnosis in our patients,
more common
1. Burns FJ. Cancer risk associated with therapeutic irradiation of skin. Arch Dermatol. 1989;125:979-981. 2. Lindel\l=o"\fB, Eklund G. Incidence of malignant skin tumors in 14140 patients after grenz-ray treatment for benign skin disorders. Arch Dermatol.
Close-up
Beverley Adriaans, MD Anthony du Vivier, MD Dermatology Department King's College Hospital
3. Mortensen AC, Kjeldsen H. Carcinomas following grenz ray treatment of benign dermatoses. Acta Derm Venereol. 1987;67:523-525. an
Denmark Hill London SE5 9RS,
Irradiated Area
To the Editor.\p=m-\Adriaans and duVivier1 recently described two patients who developed papulopustular eruptions following radiation therapy for breast carcinoma. The authors conclude that radiotherapy may induce acne vulgaris at treated sites. Since acne vulgaris is known to respond to X-ray therapy (albeit with unacceptable sequelae), their ultimate claim appears questionable, particularly since neither patient's diagnosis was confirmed by biopsy. It seems entirely possible that both patients represent instances of Grover's disease (transient acantholytic dermatosis) induced by ionizing radiation. One such patient was recently described,2 with biopsy confirmation, following radiotherapy for lung carcinoma. Other entities such as eruptive vellus hair cysts and pityrosporum folliculitis may also mimic acne on the trunk. Once again, contributors to the dermatologic literature are encouraged to support their claims with biopsy confirmation. Fixed tissue will more easily withstand the rigors of future revisionism. Jonathan L. Held, MD Department of Dermatology Nashoba Community Hospital 190 Groton Rd
Ayer, MA 01432
patient's papular eruptions.
both our patients had an excellent response to therapy, and close-up views of the eruptions were submitted (Figure) that are very convincing, but we were limited by the number of pictures we were permitted to publish.
1986;122:1391-1395.
Acne in
view of
England
Dermatologic Radiation and Cancer To the Editor.\p=m-\The editorial in the July 1989 issue of the Archives requires a response. Burns1 confuses grenz ray therapy with superficial radiation, overestimates the cancer risk following grenz ray therapy, and thereby invites confusion.
A common mistake made by Burns in this editorial is grouping grenz ray with other x-ray modalities, and it is the
purpose of this letter to report the existing risk estimates and to clarify the confusion between grenz rays and superficial x-rays. Grenz ray is defined as that x-ray having a half-value
layer between 0.016 and 0.035 mm of aluminum, or a tube voltage of from 10 to 15 kV (50% of grenz rays are absorbed by 0.5 mm of skin).2 Burns1 states, "Nevertheless, several studies have established the carcinogenicity of skin radiation therapies by conducting long-term follow-up of patients exposed to ionizing radiation in the form of low-voltage x-rays or grenz rays." The data from the Swedish study by Lindel\l=o"\fand Eklund3
Downloaded From: http://archderm.jamanetwork.com/ by a New York University User on 05/22/2015
yields a risk for squamous cell cancer of 0.2 for 10 000 per¬
per gray, not 40 per 10 000 persons per gray as stated by Burns. A total of 14 237 patients received therapeutic grenz rays sons
for therapy of benign conditions. Average follow-up time is 15 years. In 58 patients, a malignant skin tumor was diag¬ nosed more than 5 years after grenz ray therapy. Nineteen patients had malignant melanomas, and 39 patients had other malignant skin tumors. The expected number of mel¬ anomas was 17.8, and that of other malignant skin tumors was 26.9. None of the patients with malignant melanomas, and only 8 of the patients with other skin tumors, had re¬ ceived grenz ray therapy at the site of the tumor. Six of the 8 patients with other skin tumors had been exposed to other known carcinogens. Four hundred eighty-one patients re¬ ceived accumulated doses of grenz rays greater than or equal to 100 Gy on one and the same area. No malignancies were found on these areas.3 Burns' states, "The incidence of basal cell carcinomas (BCC) was estimated to be 355 per 10" persons per gray (in a follow-up study of children irradiated for tinea capitis)." Note the modality discussed here is not grenz ray but su¬ perficial radiation having an average half-value layer of 0.9 mm of aluminum produced by 100 kV of unfiltered radiation through a glass tube. Burns1 states, "The thyroid gland is one of the more ra¬ diosensitive organs in the body, and thyroid adenomas are frequently seen after head or neck irradiation." Studies at the Skin and Cancer Unit of New York (NY) University Medical Center show that a maximum of 0.06 Gy administered to 2200 children who were irradiated for tinea capitis produced six thyroid adenomas; certainly not a fre¬ quent sequelae. Also, this treatment with superficial x-rays was abandoned in the 1950s. Goldschmidt et al2 have shown that the average thyroid dose per 1000 R to the side of the face with a half-value layer of 0.75 mm of aluminum, properly shielded, is an average of 0.002 Gy. Burns' states, "Skin cancer occurs frequently enough af¬ ter grenz ray treatment for lichen sclerosus of the vulva and psoriasis of the scalp that a dosage limit of 0.5 Gy/wk is recommended." This conclusion is unfounded, based on the very fine ar¬ ticle by Lindelöf and Eklund, misquoted by Burns; 4 Gy/wk was recommended for psoriasis of the scalp." Burns' states, "The high risk of BCC following irradiation of skin with grenz rays, x-rays, or PUVA makes it doubtful that the use of such therapies can be justified for benign conditions when other effective therapies are available." In their "Literature Review of Cutaneous Neoplasms Produced by Grenz Rays in Humans" (Table 2), Lindelöf and Eklund3 record only two BCCs.3 This certainly cannot be classified as a "high risk." In both of the above cases, the dose of grenz ray therapy received by the patient is unknown. Unfortunately, basal cell carcinoma was not reported in the Swedish study as this is not a registered lesion. How¬ ever, in a follow-up study of 3531 patients by Kopf5 treated with curettage-electrodesiccation, x-ray, and excision for basal cell carcinoma, the 5-year recurrence rate was 20%, 9%, and 9%, respectively. The x-ray therapy was, in this case, superficial x-rays (half-value layer, 0.9 mm alumi¬ num). Even in the case of treatment for basal cell carci¬ noma, a recurrence rate for basal cell carcinoma at the treatment site was smaller than or equal to that for the other modalities. In summary, grenz ray therapy has not been shown to be a significant carcinogenic risk. Radiation in the grenz ray
and
superficial x-ray peutic modality.
range remains
a
very useful thera¬
Arthur H. Gladstein, MD Skin and Cancer Unit Department of Dermatology New York University Medical Center 562 First Ave New York, NY 10016
1. Burns FJ. Cancer risk associated with therapeutic irradiation of skin. Arch Dermatol. 1989;125:979-981. 2. Goldschmidt H, Gorson RO, Lassen M. Dermatologic radiotherapy and thyroid cancer: dose measurements and risk quantification. Arch Dermatol.
1983;119:383-390. 3. Lindel\l=o"\fB, Eklund G. Incidence of malignant skin tumors in 14140 patients after grenz-ray treatment for benign skin disorders. Arch Dermatol. 1986;122:1391-1395. 4. Lindel\l=o"\fB, Lagerholm B, Liden S. Skin cancer caused by grenz rays. Acta Derm Venereol (Stockh). 1988;68:275-276. 5. Kopf AW. Computer analysis of 3531 basal cell carcinomas of the skin. J Dermatol. 1979;6:267-282.
More Questions About Purpura Fulminans
To the Editor.\p=m-\Ifound the report by Auletta and Headington1 on the relation between purpura fulminans and congenital or acquired severe protein C deficiency most illuminating in a realm that had been murky before. Several additional questions arise. First, what are the histopathologic findings of the early blanchable lesions, or of those skin lesions that resolve spontaneously, quickly, and without scarring? It would be hard to invoke significant
red blood cell extravasation with these features. Could there be a reactive dilatation of thrombus-free or at least unoccluded cutaneous arterioles and venules near those filled with fibrin thrombi? Is there significant cutaneous edema, perhaps from the same mechanism, in watershed zones that do not ultimately suffer intracutaneous and subcutaneous hemorrhage and cutaneous necrosis? Have biopsies ever been performed on early or nonprogressive lesions, either in human patients or in an animal model and, if so, what have they shown? Second, it is worth noting that effective outpatient therapy of protein C deficiency with warfarin does not affect ei¬ ther of those procoagulant factors ordinarily directly inac¬ tivated by protein C, namely, factors V and VIII. Rather, warfarin down-regulates synthesis of other, more suscepti¬ ble proteins. Finally, is it known why infants who are homozygous for protein C deficiency can have a delay in the appearance of purpura fulminans? One's first impression, that the mole¬ cule is too large for transplacental transmission, cannot be correct, since larger immunoglobulin molecules are well known to cross the placenta. Given a plasma half-life of only 8 hours for protein C, it seems remarkable that even with intrauterine transplacental "loading," any homozygousdeficient infant would not develop severe symptoms within the first 4 half-lives, let alone 15 as in the case described here! Henry Schneiderman, MD Room CG-058 University of Connecticut Health Center Farmington, CT 06032-9984 1. Auletta MJ, Headington JT. Purpura fulminans: a cutaneous manifestation of severe protein C deficiency. Arch Dermatol. 1988;124:1387\x=req-\ 1391.
Downloaded From: http://archderm.jamanetwork.com/ by a New York University User on 05/22/2015
