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Complications of microwave hyperthermia treatment of psoriasis
Therapv Complications of microwave hyperthermia treatment of psoriasis Jill Keddy-Grant, MD,a Sylvia Garnis-Jones, MDCM, FRcpC,a John Adam, MD, FRcpC,a Cyril Danjoux, MD, FRCPC,b Lee Gerig, PhD,b Avner Ginsburg, BSc(Eng),b Ronald Mitchel, PhD,c and Peter Raaphorst, PhDb
Ottawa and Chalk River, Ontario, Canada Three healthy men with psoriatic plaques unresponsive to tar, anthralin, and UVB were treated with 2450 MHz microwave heating for 30 minutes at 42° C. Two patients had plaques over bony prominences. Pain developed in both patients, and one had a hypotensive episode during the first treatment. The third patient, whose plaque was greater than 2 em and was not located over a bony prominence, completed the 5 weeks of biweekly treatments with complete resolution of the plaque and no complications. (J AM ACAD DERMATOL 1990; 22:651-3.)
Hyperthermia combined with chemotherapy and radiation is being evaluated as a treatment for cancer. I-3 Its use dates from the early 1970s, when Overgaard and Overgaard4 and later Marmor et al. 5 reported the use of heat alone as a means oflocal tumor control. Hyperthennia was first used for psoriasis by Orenberg et a1. 6 Plaques were heated to 42° to 45° C for 30 minutes three times weekly for a total of four to ten treatments. Of 22 plaques, 15 cleared completely but then relapsed within 3 months. Two patients had a sensation of pressure and focal "deep heating" within plaques located over bone. Urabe et a1. 7 reported that of 19 patients were successfully treated with contact heating pads. Skin surface temperature was elevated to 42° to 43° C. The average time required for complete regression in the heat-treated area was 27 days, compared with 44 days with the Goeckerman regimen. The Ottawa Regional Cancer Center has a wellestablished microwave hyperthermia system for the treatment of superficial tumors. 8 We report its use in the treatment of chronic plaque-type psoriasis.
From Ottawa Civic Hospital" and Ottawa Regional Cancer Center (Ontario Cancer Foundation),b and Atomic Energy of Canada Limited, Chalk River." Reprint requests: Sylvia Garnis-Jones, MD, Division of Dermatology, Ottawa Civic Hospital, 1053 Carling Ave., Ottawa, Ontario KI Y 4E9, Canada.
16/1/14318
PATIENTS AND METHODS Subjects. Three men, aged 43, 58, and 65 years, with chronic plaque-type psoriasis vulgaris gave informed consent and then entered the study. All had chronic psoriasis and had been treated with a variety of standard treatments. A single discrete plaque, 2 to 10 em in diameter, on a limb, was randomly chosen as a test site. These areas had not been treated for I month. Treatment protocol. The lesions were heated to 43 to 45 0 C for 30 minutes twice weekly for 5 weeks. A 19-9auge Teflon-coated catheter was inserted intradermally beneath the plaque 1 day before the first treatment. A microprobe was inserted into the catheter to obtain a thermal profile at about 0.5 em at the deepest point. Other probes were placed on the skin surface in an array and were taped with 0.5 em thick Superflab bolus material (Mick Radio-Nuclear Instruments, Bronx, N.Y.) to assure good contact. The plaque was evaluated before treatment, at the fifth treatment, at the last treatment, and 3 months after treatment. Plaque heat dosimetry. The hyperthermia thermometry and control system is described elsewhere.8 It consists of a computerized data acquisition and control system, a microwave generator and antenna, and specially developed thermocouple microprobes. The generator operated at 2.45 GHz, and a maximum power of 100 W could be obtained. 0
RESULTS The first patient had a erythematous, 4 X 3 cm plaque on the left shin. The first two treatments were uneventful except for mild discomfort caused by the intradermal probe. On the third visit the patient
651
652
Journal of the American Academy of Dermatology
lfeddy-GrantetaL
...
'
Fig. 1. Psoriatic plaque on thigh after catheter insertion.
Fig. 2. Resolution of plaque without recurrence 3 months after treatment.
noted a deep ache at the treatment site and would not complete the treatment. The second patient had an erythematous, 8 X 4 em plaque on the left elbow. Fifteen minutes into the first treatment he noted deep pain and became diaphoretic and hypotensive. He recovered within 10 minutes but continued to feel pain at the treatment site for another 3 days. The third patient had a2.0 X 1.4 em plaque of the right upper part of the thigh (Fig. 1). He tolerated the treatment well, and the plaque resolved. After 3 months no evidence of recurrence was observed (Fig. 2).
DISCUSSION
Our results indicate that localized microwave hyperthermia for psoriasis can have significant side effects, especially if the plaques are located directly over bone. The temperature increase produced in different tissue layers depends on the dielectric property, how well the tissue is supplied with blood vessels, and on the extent to which blood flow carries heat away.9,lO Cook ll has shown that tissue heating will lead to pain when nerve endings approximately 1.5 mm below the skin reach a temperature of 46° C. Bone is known to be a poor thermal conductor. 10 It is possible that the bone tem-
Volume 22 Number 4 April 1990
Complications ofmicrowave hyperthermia treatment 653
perature beneath the treatment sites reached 46° C. Hypotension subsequent to deep pain suggests that thermoregulatory mechanisms adapt to thermal loads caused by microwave irradiation. The hypothalamus integrates central and peripheral thermosensory signals of the thermal state of the organism and organizes effects or activities such as diaphoresis, shivering, and hypotension. Michaelson 12 pointed out that temperature-sensitive nerve endings in the skin and other peripheral tissues signal temperature-sensitive neurons within the brain stem, mainly in the hypothalamus. Therefore the cutaneous perceptions of deep pain may be a warning to prevent injurious exposure. Only one patient experienced hypotension. This finding suggests that warning effector mechanisms are evoked only by power densities that lie somewhere between the levels required for evoking cutaneous sensations and for evoking pain sensation. Ifhyperthermia is to be used to treat benign hyperproliferative skin disease, more information will be needed to define its range of safety. REFERENCES 1. Dewey WC, Hopwood LE, Sapareto SA, et al. Cellular responses to a combination of hyperthermia and radiation. Radiology 1977; 123 :464-77.
2. Hornback NB. Clinical hyperthermia experience. In: Hyperthermia and cancer: human clinical trial experience. Boca Raton, Fla.: CRC Press, 1984:73-116. 3. Bull JMC. An update On the anticancer effects of a combination of chemotherapy and hyperthermia. Cancer Res 1984;44:4853-6. 4. Overgaard K, Overgaard J. Investigations on the possibilityofa thermic tumor therapy II. Eur J Cancer 1972;8:573-
5. 5. Marmor J, Hahn N, Hahn G. Tumor cure andceUsurvival after localized radiofrequency heating. Cancer 1977; 37:879-83. 6. Orenberg EK, Deneau DG, Farber E. Response of chronic psoriatic plaques to localized heating induced by ultrasound. Arch DermatoI1980;1l6:893-7. 7. Urabe H, Nishitani K, Kokda H. Hyperthermia in the treatment of psoriasis. Arch Dermatol 198 L; 117:770-4. 8. Gerig LH, Danjoux CE, Raaphorst GP, et al. A computerized thermocouple-based clinical thermometer system. Endocurie Hypertherm OncoI1988;4:31-7. 9. Asserheim HM, Hill PA, Preston E, et aL The biological effects of radio-frequency and microwave radiation. National Research Council of Canada, 1988:154-5. Publication of the Environmental Secretariat. 10. Fajardo LF. Pathological effects ofhyperthermia in normal tissues. Cancer Res 1984;44:4826-35. 11. Cook HF. The pain threshold for microwave and infra-red radiation. J Physiol (Land) 1952;118:1-11. 12. Michaelson SM. Cutaneous perception of microwaves. J Microw Power 1972;7:67-73.
Ottawa and Chalk River, Ontario, Canada Three healthy men with psoriatic plaques unresponsive to tar, anthralin, and UVB were treated with 2450 MHz microwave heating for 30 minutes at 42° C. Two patients had plaques over bony prominences. Pain developed in both patients, and one had a hypotensive episode during the first treatment. The third patient, whose plaque was greater than 2 em and was not located over a bony prominence, completed the 5 weeks of biweekly treatments with complete resolution of the plaque and no complications. (J AM ACAD DERMATOL 1990; 22:651-3.)
Hyperthermia combined with chemotherapy and radiation is being evaluated as a treatment for cancer. I-3 Its use dates from the early 1970s, when Overgaard and Overgaard4 and later Marmor et al. 5 reported the use of heat alone as a means oflocal tumor control. Hyperthennia was first used for psoriasis by Orenberg et a1. 6 Plaques were heated to 42° to 45° C for 30 minutes three times weekly for a total of four to ten treatments. Of 22 plaques, 15 cleared completely but then relapsed within 3 months. Two patients had a sensation of pressure and focal "deep heating" within plaques located over bone. Urabe et a1. 7 reported that of 19 patients were successfully treated with contact heating pads. Skin surface temperature was elevated to 42° to 43° C. The average time required for complete regression in the heat-treated area was 27 days, compared with 44 days with the Goeckerman regimen. The Ottawa Regional Cancer Center has a wellestablished microwave hyperthermia system for the treatment of superficial tumors. 8 We report its use in the treatment of chronic plaque-type psoriasis.
From Ottawa Civic Hospital" and Ottawa Regional Cancer Center (Ontario Cancer Foundation),b and Atomic Energy of Canada Limited, Chalk River." Reprint requests: Sylvia Garnis-Jones, MD, Division of Dermatology, Ottawa Civic Hospital, 1053 Carling Ave., Ottawa, Ontario KI Y 4E9, Canada.
16/1/14318
PATIENTS AND METHODS Subjects. Three men, aged 43, 58, and 65 years, with chronic plaque-type psoriasis vulgaris gave informed consent and then entered the study. All had chronic psoriasis and had been treated with a variety of standard treatments. A single discrete plaque, 2 to 10 em in diameter, on a limb, was randomly chosen as a test site. These areas had not been treated for I month. Treatment protocol. The lesions were heated to 43 to 45 0 C for 30 minutes twice weekly for 5 weeks. A 19-9auge Teflon-coated catheter was inserted intradermally beneath the plaque 1 day before the first treatment. A microprobe was inserted into the catheter to obtain a thermal profile at about 0.5 em at the deepest point. Other probes were placed on the skin surface in an array and were taped with 0.5 em thick Superflab bolus material (Mick Radio-Nuclear Instruments, Bronx, N.Y.) to assure good contact. The plaque was evaluated before treatment, at the fifth treatment, at the last treatment, and 3 months after treatment. Plaque heat dosimetry. The hyperthermia thermometry and control system is described elsewhere.8 It consists of a computerized data acquisition and control system, a microwave generator and antenna, and specially developed thermocouple microprobes. The generator operated at 2.45 GHz, and a maximum power of 100 W could be obtained. 0
RESULTS The first patient had a erythematous, 4 X 3 cm plaque on the left shin. The first two treatments were uneventful except for mild discomfort caused by the intradermal probe. On the third visit the patient
651
652
Journal of the American Academy of Dermatology
lfeddy-GrantetaL
...
'
Fig. 1. Psoriatic plaque on thigh after catheter insertion.
Fig. 2. Resolution of plaque without recurrence 3 months after treatment.
noted a deep ache at the treatment site and would not complete the treatment. The second patient had an erythematous, 8 X 4 em plaque on the left elbow. Fifteen minutes into the first treatment he noted deep pain and became diaphoretic and hypotensive. He recovered within 10 minutes but continued to feel pain at the treatment site for another 3 days. The third patient had a2.0 X 1.4 em plaque of the right upper part of the thigh (Fig. 1). He tolerated the treatment well, and the plaque resolved. After 3 months no evidence of recurrence was observed (Fig. 2).
DISCUSSION
Our results indicate that localized microwave hyperthermia for psoriasis can have significant side effects, especially if the plaques are located directly over bone. The temperature increase produced in different tissue layers depends on the dielectric property, how well the tissue is supplied with blood vessels, and on the extent to which blood flow carries heat away.9,lO Cook ll has shown that tissue heating will lead to pain when nerve endings approximately 1.5 mm below the skin reach a temperature of 46° C. Bone is known to be a poor thermal conductor. 10 It is possible that the bone tem-
Volume 22 Number 4 April 1990
Complications ofmicrowave hyperthermia treatment 653
perature beneath the treatment sites reached 46° C. Hypotension subsequent to deep pain suggests that thermoregulatory mechanisms adapt to thermal loads caused by microwave irradiation. The hypothalamus integrates central and peripheral thermosensory signals of the thermal state of the organism and organizes effects or activities such as diaphoresis, shivering, and hypotension. Michaelson 12 pointed out that temperature-sensitive nerve endings in the skin and other peripheral tissues signal temperature-sensitive neurons within the brain stem, mainly in the hypothalamus. Therefore the cutaneous perceptions of deep pain may be a warning to prevent injurious exposure. Only one patient experienced hypotension. This finding suggests that warning effector mechanisms are evoked only by power densities that lie somewhere between the levels required for evoking cutaneous sensations and for evoking pain sensation. Ifhyperthermia is to be used to treat benign hyperproliferative skin disease, more information will be needed to define its range of safety. REFERENCES 1. Dewey WC, Hopwood LE, Sapareto SA, et al. Cellular responses to a combination of hyperthermia and radiation. Radiology 1977; 123 :464-77.
2. Hornback NB. Clinical hyperthermia experience. In: Hyperthermia and cancer: human clinical trial experience. Boca Raton, Fla.: CRC Press, 1984:73-116. 3. Bull JMC. An update On the anticancer effects of a combination of chemotherapy and hyperthermia. Cancer Res 1984;44:4853-6. 4. Overgaard K, Overgaard J. Investigations on the possibilityofa thermic tumor therapy II. Eur J Cancer 1972;8:573-
5. 5. Marmor J, Hahn N, Hahn G. Tumor cure andceUsurvival after localized radiofrequency heating. Cancer 1977; 37:879-83. 6. Orenberg EK, Deneau DG, Farber E. Response of chronic psoriatic plaques to localized heating induced by ultrasound. Arch DermatoI1980;1l6:893-7. 7. Urabe H, Nishitani K, Kokda H. Hyperthermia in the treatment of psoriasis. Arch Dermatol 198 L; 117:770-4. 8. Gerig LH, Danjoux CE, Raaphorst GP, et al. A computerized thermocouple-based clinical thermometer system. Endocurie Hypertherm OncoI1988;4:31-7. 9. Asserheim HM, Hill PA, Preston E, et aL The biological effects of radio-frequency and microwave radiation. National Research Council of Canada, 1988:154-5. Publication of the Environmental Secretariat. 10. Fajardo LF. Pathological effects ofhyperthermia in normal tissues. Cancer Res 1984;44:4826-35. 11. Cook HF. The pain threshold for microwave and infra-red radiation. J Physiol (Land) 1952;118:1-11. 12. Michaelson SM. Cutaneous perception of microwaves. J Microw Power 1972;7:67-73.