Lasers in Surged and Medicine 4: 73-77

Lasers in Surged and Medicine 4: 73-77 (1984)

Response of Psoriasis to Red Laser Light (630 nm) Following Systemic Injection of 
Hematoporphyrin Derivative

Michael W. Berns, PhD, Mark Rettenmaier, MD, Jerry McCullough, PhD, Joan Coffey, RN, Alan Wile, MD, Michael Berman, MD, Philip DISala, MD, and Gerald Weinstein, MD

Departments of Surgery, (M. W.B.,J.C.,A.W), Obstetrics and Gynecology (M.R.,M.B.,P.D.), and Dermatology (J. M., G. W.), University of Califomia, Itvine

Systemically injected hematoporphyrin derivative (HPD) in combination with red laser light (630 nm) was used to treat a patient with intraepithelial neoplasia of the vulva. Since the patient had psoriasis in the mons pubis area this region also was exposed to the red light. The psoriasis treatment area was divided into nvo regions receiving 40 and 20 J/cm . Both psoriatic zones responded vigorously to the HPD + light treatment, forming eschars by I week postirradiation All three treatment zones (the neoplastic area and the two psoriatic areas) underwent normal re- epithelializa_ion by 17 days.

Key words: psoriasis, hematoporphyrin, laser, cancer

INTRODUCTION

The selective retention of hematoporphyrin derivative (HPD) by malignant tissue following intravenous injection has led to its use in the treatment of a wide variety of malignancies [1,2] including skin cancer. [3]. Exposure of cancer cells that contain HPD to an appropriate wavelength of light results in photochemical events that bring about rapid cell death [1,2]. As early as 1936 [4], it was suggested that hematoporphyrin in combination with ultraviolet (UVA) light could be effective in controlling hyperproliferative skin disease, such as psoriasis More recently two reports have appeared [5,6] in which hematoporphyrin in combination with UVA has been used to treat psoriasis. Our results over the last 2 years employing longerwavelength red light (625-630 nm) to treat over 100 patients for various malignancies [2] has suggested that hematoporphyrin derivative-photoradiation therapy (HPD-PRT) with visible light could be effective in the control of proliferative skin diseases. In this report we describe the treatment of psoriatic lesions by HPD-PRT in a patient with intraepithelial neoplasia of the vulva. Address reprint requests to Dr. Michael w. Berns, Director of Laser Clinical services, Department of Surgery, university of California, Irvine, Irvine, CA 92717.

r) 1984 Alan R. Liss, Inc.

MATERIALS AND METHODS

A 36-year-old caucasian woman was initially seen by the dermatology department for treatment of psoriasis for which she had been receiving methotrexate systemically for over 15 years. Routine pelvic examination showed multifocal hyperpigmented vulvar lesions and several areas of superficial ulceration. The patient was referred to the department of obstetrics and gynecology for further evaluation. Histologcial analysis of multifocal vulvar biopsies showed vulvar intraepithelial neoplasia (VIN).

The patient subsequently underwent skinning vulvectomy and placement of a split thickness skin graft [7] in September 1982. She was presented again in January 1983 with a 2-cm-diameter focal vulvar lesion outside of the skin graft that was histologically identified as VIN. At that time the option of entering our HPD-PRT experimental protocol for treatment of VIN was presented to the patient. The patient elected to enter the HPD-PRT program and at the same time the patient agreed to have two 2-cm-diameter regions of psoriatic tissue in the adjacent mons pubis exposed to the treatment light.

The method for HPD-PRT treatment followed the standard procedure described elsewhere [2]. The patient was injected with an intravenous (IV) bolus of HPD (obtained from ORD, Inc. Cheektowaga, NY) at a dose of 3mg HPD/kg of body weight. The patient was cautioned to avoid bright light and was provided with detailed written instructions to stay out of bright light (including normal sunlight) for up to I month following injection. These precautions are necessary to avoid a photosensitivity reaction manifest by erythema and edema of the skin. At 72 hours post injection, the patient returned to the outpatient clinic for light treatment. The red light source (630 nm) was a rhodamine-B dye laser (SpectraPhysics Model #375) excited by a 12-W argon ion laser (SpectraPhysics Model #171) emitting 6 W at 514 nm. The dye laser beam (red light at 630 nm ) was focused into a 400-p4m quartz fiber optic. The other end of the fiber optic (about 15 feet away) was positioned over the desired treatment area so that the light emanating from the tip covered the entire treatment zone. Output from the fiberoptic tip was measured with a Scientech #354 colorimeter and the dye laser wavelength was determined using a JY 5-354 monochrometer. The 2-cm diameter areas to be treated were carefully measured and marked with a black marking pen (Fig. 1). When fashioning the treatment zones, we were careful to include some normal (nonpsoriatic and non-VIN-involved) tissue within the treatment zone. The VIN area (Zone #3 in Figures) was treated with a total light dose of 40 J/cm2, a dose rate of 127mW/cm2, and a total treatment time of 5.2 minutes. The dose and dose rate were based upon results with previous patients. One psoriatic region (#1) was treated at the same dose parameters (40 J/cm2), and the other psoriatic region (#2) was given a lower total dose (20 J/cm2).

RESULTS

The patient experienced no unusual physical effects during light treatment, though other patients (about 20-30%) indicated an "itching" or "tingling" sensation during the actual light exposure. The patient returned to the outpatient clinic for follow-up examination at 3 days, 7 days, 17 days, and 53 days following laser exposure.

~ - Rt 3 days posttreatment (Fig. 2), all three treatment areas~d~ reddening and tissue necrosis, but only in the diseased portions of the 2-cm spot (VIN-involved or psoriatic tissue). The noninvolved skin within the treatment circle appeared perfectly normal in all three areas, though some slight erythema was evident in the normal skin in area #1. The only discomfort to the patient was a feeling of moderate sunburn in the treatment areas for 48 hours following laser exposure. At 7 days postlaser (Fig. 3), the area of VIN appeared to be resolving with considerable re-epitheliazation. A slight erythema was evident around the margin of the responding area. Psoriasis area #1 exhibited re-epithelialization around a central dark eschar region. The lower dose psoriatic area (#2) appeared to have re-epithelialization in the top portion of the affected area and a small eschar in the lower portion. By 17 days (Fig. 4) all three treatment zones exhibited extensive re-epithelialization. There was no longer evidence of eschars in psoriatic areas #1 and #2. The psoriatic area (#2) receiving the lower light dose (20 J/cm2) appeared pinkish with clearing evident in the center. The psoriatic area receiving the higher light dose (40 J/cm2) appeared devoid of psoriatic tissue. At 56 days posttreatment (no photos available), all the lesions had healed normally.

DISCUSSION

Though the occurrence of both neoplasia and psoriasis simultaneously in the pubic area is quite unusual, this case has permitted confirmation of the earlier suggestion [4-6] that hematoporphyrin (and HPD) in combination with light can cause selective destruction of psoriatic tissue without harming surrounding or deeper normal tissue. Apparently, HPD is selectively retained by psoriatic tissue as well as neoplastic tissue. The case reported here differs from the previous psoriasis reports in that the wavelength of light employed was red (630 nm) rather UVA. E3y employing laser sources, the intensity of light can be of sufficient magnitude to permit treatment of relatively large areas in a short period of time, or smaller discrete fields through the use of fiber optics as reported here. In addition, the argon laser-dye combination can deliver visible and ultraviolet wavelengths at 365 nm, 488 nm, 514 nm, and 630 nm. This device in ( combination with UVA sources makes available a wide spectrum of wavelengths than penetrate tissue from just a few cell layers to up to I centimeter.

If red ligh: (or other visible wavelengths, such as green), in combination with HPD, is effectil We in controlling psoriasis, a method considerably less carcinogenic that psoralen-UAi'A (PUVA) may be available. Considering the known adverse genetic effects (carcinogenic) of PUVA, the use of a visible light source with a drug (HPD) that does not bind to DNA (as opposed to psoralen) may have a substantial advantage over current conventional therapy. The major contraindication of this approach is general light sensitivity for up to 30 days post-HPD injection. This can be of considerable inconvenience to the patient, and can result in severe sunburn and edema. Furthermore, the nature of the retention and location of HPD that leads to the prolonged light sensitivity is not understood. The development of a topical formulation for localized HPD application is currently in progress [83 and should greatly expand the use of HPD-PRT in the treatment of psoriasis and other hyperproliferative disorders. Finally, the doses of light used in the case reported here t20 and 40 J/cm2) are probably too high. This is evidenced by the eschar formation, which suggests tissue destruction at a greater depth than necessary. The use of a lower light dose in combination with a topical formulation of HPD could be a promising mode of therapy.

ACKNOWLEDGMENTS

This research was supported by National Institutes of Health Grants CA 32248, RRO 1192, GM 23445, and AM 27110.

REFERENCES

1. Dougherty TJ, Kaufman JE, Goldfarb A, Weishaupt KR, Boyle D, Mittleman A: Photoradiation therapy for the treatment of malignant tumors. Cancer Res 38:2628-2635, 1978.
2. Dahlman A, Wile AG, Bums RG, Mason GR, Johnson F. Berns MW: Laser photoradiation therapy of cancer. Cancer Res 43:430-434, 1982.
3. Dougherty TJ: Photoradiation therapy of cutaneous and subcutaneous malignancies. J Invest Dermatol77:122-124, 1981.
4. Silver H: Psoriasis vulgaris treated with hematoporphyrin. Arch Dermatol Syphilol 36:1118-1119, 1937.
5. Diezel W. Meffert H. Sonnichsen N: Therapy of psoriasis with hematoporphyrin derivate and light. Dermatol Monatsschr 166:599, 1980.
6. Diezel W. Sonnichsen N. Meffert H: Treatment of psoriasis with hematoporphyrin derivate and longwave ultraviolet light. Stud Biophys (in press).
7. Rutlege F. Sinclair F: Treatment of intraepithelial carcinoma of the vulva by skin excision and graft. Am J Obstet Gynecol 102:806, 1968.
8. McCullough JL, Weinstein GD, Lemus LL, Rampone W. Jenkins J: Development of a topical Hematoporphyrin derivative formulation: Characterization of photosensitizing effects in vivo. J Invest Dermatol 81: 528-532, 1983.

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