PLAQUE TARGETED SUB-BLISTERING DOSIMETRY

Abstract

A method for testing diseased skin for treatment of the diseased skin, comprising the steps of administering a plurality of increasing doses of phototherapy directly to regions of an area of diseased skin and analyzing the area of the diseased skin to assess the doses at which burning and blistering of the diseased skin occurs, determining a maximum dose of phototherapy that can be administered to the diseased skin based on the assessment of the doses at which the burning and the blistering of the diseased skin occurs, and treating the diseased skin.

Claims

1. A method for treating a skin disease, comprising the following steps: administering a plurality of doses of phototherapy at increasing intervals to area of diseased skin; analyzing the area of the diseased skin and assessing the doses at which burning and blistering of the diseased skin occurs; determining a maximum dose of phototherapy that can be administered to the diseased skin based on the assessment of the doses at which the burning and the blistering of the diseased skin occurs; and treating the diseased skin below or at the maximum dose.

2. The method of claim 1, wherein the diseased skin is psoriasis.

3. The method of claim 1, further comprising the step of treating the diseased skin at approximately about at least one of at a minimal blistering dose, at one or two levels below a minimal blistering dose or at about a minimal erythema dose.

4. The method of claim 1, further comprising the step of marking the area of diseased skin prior to administering the plurality of doses of phototherapy and then administering the doses of phototherapy within the markings.

5. The method of claim 1, wherein eight doses of increasing phototherapy are administered to eight region of diseased skin.

6. The method of claim 1, wherein nine doses of increasing phototherapy are administered to nine region of diseased skin.

7. The method of claim 1, further comprising the step of determining the minimal erythema dose applied to the area of the diseased skin after the step of administering the plurality of doses of phototherapy.

8. The method of claim 1, further comprising the step of determining the minimal blistering dose applied to the patch of diseased skin after the step of administering the plurality of doses of phototherapy.

9. The method of claim 1, further comprising the step of waiting about 24 to 48 hours after administering the plurality of doses of phototherapy and then analyzing and assessing the area of diseased skin to determine an upper dosing limit that should be used to treat the patient.

10. The method of claim 1, further comprising the step of applying a light-sensitizing agent to the area of diseased skin.

11. The method of claim 1, further comprising the step of applying a topical spray or ointment to the area of the diseased skin to minimize phototoxicity.

12. The method of claim 1, further comprising the step of treating the diseased skin by applying at most three doses of phototherapy to place the diseased skin into remission.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIG. 1A illustrates testing of a plurality of spots with various dosage levels;

[0016] FIG. 1B illustrates an embodiment of dosage interval levels for the plurality of spots in FIG. 1A;

[0017] FIG. 2 shows the effect of a dose of phototherapy applied directly to an area of diseased skin at which the skin reacts with minimal erythema (i.e., Minimal Erythema Dose);

[0018] FIG. 3 shows the effect of a dose of phototherapy applied directly to an area of diseased skin at which blistering occurs (i.e., Minimum Blistering Dose); and

[0019] FIG. 4 shows the dose at which a patient's skin reacts with minimal erythema and the dose at which blistering occurs.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0020] As discussed above, known phototherapy treatment of skin disorders (e.g., psoriasis) involves testing non-affected areas of a patient's skin tissue by applying doses of varying levels of UV light in an attempt to determine the patient's maximum tolerable dose. However, diseased skin, has a much higher tolerance to UV light than non-affected skin. Thus, testing non-affected areas of skin does not provide an accurate assessment of the patient's tolerance and in turn maximum dosage that can be applied to a region of the patient's skin that is affected by a skin disorder.

[0021] FIGS. 1-3 illustrate an embodiment of a method of testing a region of skin affected by a skin disorder prior to phototherapy treatment by applying dosages of incremental wavelengths of UV light directly to the region of skin affected by the skin disorder that is designated hereinafter by reference numeral 10. In an embodiment, the skin disorder is psoriasis.

[0022] UV phototherapy utilizes light in the UVB band, which extends in wavelength between about 280 nanometers and about 320 nanometers. Psoriasis-afflicted tissue can be effectively rehabilitated with light having wavelengths between about 300 nanometers and about 310 nanometers. Light having a wavelength spectrum between about 295 nanometers and about 325 nanometers can be effective in healing the tissue as well. However, due to the intensity of the light applied to a patient, there is a risk of some undesirable side effects of phototherapy to treat psoriasis and other skin conditions such as DNA damage (e.g., skin cancer). Therefore, to treat diseased skin and joints of a subject under conditions that can maximize a likelihood of placing the diseased tissue into remission while minimizing the risk of erythema and/or DNA damage, a physician will typically treat a patient in a range of between about 295 nanometers and about 320 nanometers, more specifically, between about 300 nanometers and about 310 nanometers, and even more specifically at about 308 nanometers.

[0023] The fluence of light having wavelengths distributed between about 300 and about 310 nanometers has been determined to range between about 500 mJ/cm.sup.2 and about 5000 mJ/cm.sup.2. More specifically, the fluences preferably range between about 100 mJ/cm.sup.2 and about 8 J/cm.sup.2, and between about 300 mJ/cm cm.sup.2 and about 3 J/cm cm.sup.2. Other dosages are also possible depending upon where blistering of the plaque takes place. To determine such blistering the laser radiation may be applied in increments of typically 50, 100 or 200 mJ/cm.sup.2. In an embodiment, one or two such treatments can provide significant improvement of the afflicted area of skin as opposed to 20 treatments by prior methodology.

[0024] In embodiments, phototherapy comprises an average power of between about 0.3 watts and about 0.5 watts, between about 2 watts and about 3 watts, between about 2.5 watts and about 4.5 watts, or between about 4.8 watts and about 7.2 watts. Other average powers are also possible (e.g., 10 watts or more). In embodiments, phototherapy comprises energy between about 8 mJ/pulse and about 15 mJ/pulse or between about 12 mJ/pulse and about 18 mJ/pulse. Other pulse energies are also possible based on the power of the laser and the exposure area.

[0025] In embodiments, phototherapy comprises a repetition rate of between about 50 pulses/second (Hz) and about 100 Hz (e.g., about 92 Hz), between about 100 Hz and about 500 Hz. In embodiments, the repetition rate is between about 125 Hz and about 175 Hz (e.g., about 154 Hz), between about 150 Hz and about 300 Hz (e.g., about 200 Hz, about 225 Hz, about 250 Hz), or between about 350 Hz and about 450 Hz (e.g., about 400 Hz). In an embodiment, other repetition rates are possible and higher repetition rates may reduce the treatment duration, for example, because the phototherapy device may able to deliver the treatment dosage in a shorter period of time depending on the power per pulse.

[0026] As shown in FIGS. 1A and 1B, a region of an appendage affected by psoriatic plaque is marked with a plurality of circles for pre-treatment phototherapy testing. In an embodiment, nine regions are tested at increasing intervals. However, the number of regions of diseased tissue tested can vary, for example, depending on the size of the affected region of diseased tissue or previously known treatment tolerances. After marking the regions of diseased tissue, a laser can be used to “serial test” the marked regions by apply increasing doses of UV light in the marked regions to the diseased tissue (see FIG. 1B). After applying varying levels of UV light to the psoriatic plaque diseased area, the patient is then typically sent home for about 24 to 48 hours. After 24 to 48 hours, the patient then returns to the treatment center where the area of diseased skin tissue is observed to assess the dosage level at which burning (MED) 12 and/or blistering (MBD) 14 of the diseased skin tissue begins to occur.

[0027] By observing the MED 12 as shown in the appendage in FIGS. 2 and 4 where a region of reddened skin is present and the MBD 14, as shown in FIGS. 3 and 4, where the treated region of diseased skin begins to blister, the “upper limit” dose that can be used to treat the patient can be determined. Based on the MBD, depending on the patient's tolerance and the severity of diseased tissue, among other factors, the patient can be treated at the MBD, just below the MBD (e.g., one or two dosage levels below the MBD), or closer to the MED of the diseased skin tissue.

[0028] Exposing a psoriatic area to high doses of UV light will cause faster clearing and place the skin condition into remission much faster and for a longer period of time than a lower dosage of UV light. As such, by directly testing diseased skin tissue to assess the optimal dose of laser treatment of psoriasis based on MBD allows for treatment to be close to the most aggressive and, therefore, more efficacious, but still well-tolerable dosage.

[0029] By treating a patient at or near their MBD, the number of treatment sessions required to place the diseased tissue into remission can be greatly reduced, and in an embodiment, such reduction in the number of treatments may achieve the desired result and yet decrease the total quantity or cumulative deposition of UVB light to which skin is exposed.

[0030] The risk of erythema, skin cancer and skin damage generally associated with premature aging depends the total number of photons or amount of UVB radiation directed on the skin. As such, raising the dosage in a single treatment, a couple treatments, or a few treatments can reduce the number of treatment sessions and result in a lower overall number of absorbed photons or UVB radiation, thereby reducing the risk of cancer and other skin damage. A fewer number treatments can also result in a significant reduction in hyperpigmentation that would normally be experienced due to the body's sun tanning response after each treatment. Additionally, lower numbers of treatments may also provide a higher degree of compliance of a subject to an otherwise difficult regimen involving a significant number of visits to the physician.

[0031] To treat the diseased skin, after assessing a patient's tolerance, in an embodiment, ultraviolet light is delivered to each affected region of the body, for example, by an excimer laser, as described in U.S. Pat. Nos. 7,144,248 and 7,276,059, each herein incorporated by reference in their entirety. In an embodiment, UV lamps, intense pulsed light (“IPL”) devices, light-emitting diode (“LED”) devices (e.g., available from Photo Therapeutics, Ltd. of Altrincham, United Kingdom and Photo Therapeutics, Inc. of Carlsbad, Calif.), or other phototherapy devices that are known or will be developed in the future can be employed to generate the UV light.

[0032] In an embodiment, ultraviolet light is directed only onto the affected regions. In an embodiment, ultraviolet light is directed onto the lesional as well as surrounding paralesional tissue, which although appearing normal is diseased tissue.

[0033] In an embodiment, phototherapy treatment of diseased psoriatic plaque can be combined with the use of a topical spray and/or ointment, such as clobetasol spray and calcitriol ointment to minimize phototoxicity. The use of a topical spray and/or ointment is typically used for the treatment of moderate-to-severe generalized psoriasis.

[0034] In some embodiments, phototherapy is administered or received without any help from a light-sensitizing agent. Alternatively, in an embodiment, light-sensitizing agents may be used, for example to increase the sensitivity of a cell to UV. In certain such embodiments, one or more light-sensitizing agents may be applied to the subject or received by the subject before or after phototherapy. Examples of light-sensitizing agents include, but are not limited to, coal tar, psoralen, acitretin, and salicylic acid. By avoiding treatment of unaffected portions of skin, the dosage can be raised well above conventional dosages as the affected areas will tolerate substantially higher doses without increased risk of side effects.

[0035] In an embodiment, an excimer laser can be used to generate short high power pulses of light having a wavelength of about 308 nanometers. These pulses can be high in peak power, e.g., about half a million watts, but short in duration, for example, lasting much less than about 100 nanoseconds (e.g., about 30 nanoseconds). The laser, however, may produce a plurality of such pulses at a repetition rate of about 100, 150, 200, 250, 300, 400, 450, or 500 Hz, and ranges therebetween. Tissue exposed to a plurality of these short pulses will increase in temperature slightly with application of each pulse. The cumulative effect of the plurality of pulses to raise the temperature of the tissue to a certain amount depends in part on the heat capacity of the tissue. The energy from the laser may be spread over a long enough period of time so as to permit sufficient dissipation to avoid excessive build-up of heat from the plurality of short pulses. Thermal damage caused by raising the temperature of the skin above, for example, the blister temperature of 50° C., can thereby be reduced, mitigated, or prevented. The duration of exposure of the affected tissue to the therapeutic doses of UV light, however, depends on the particular dose level.

[0036] In an embodiment, high doses of UV illumination are directed to an area of skin that is between about 25 cm.sup.2 and about 6,000 cm.sup.2, between about 25 cm.sup.2 and about 5,000 cm.sup.2, between about 25 cm.sup.2 and about 4,000 cm.sup.2, between about 25 cm.sup.2 and about 3,000 cm.sup.2, between about 25 cm.sup.2 and about 2,000 cm.sup.2, between about 25 cm.sup.2 and about 1,800 cm.sup.2, between about 25 cm.sup.2 and about 1,600 cm.sup.2, between about 25 cm.sup.2 and about 1,400 cm.sup.2, between about 25 cm.sup.2 and about 1,200 cm.sup.2, between about 25 cm.sup.2 and about 1,000 cm.sup.2, between about 25 cm.sup.2 and about 800 cm.sup.2, between about 25 cm.sup.2 and about 600 cm.sup.2, between about 25 cm.sup.2 and about 500 cm.sup.2, between about 25 cm.sup.2 and about 400 cm.sup.2, between about 25 cm.sup.2 and about 300 cm.sup.2, between about 25 cm.sup.2 and about 200 cm.sup.2, between about 25 cm.sup.2 and about 100 cm.sup.2, between about 25 cm.sup.2 and about 50 cm.sup.2, between about 1 cm.sup.2 and about 25 cm.sup.2, between about 2,000 cm.sup.2 and about 5,000 cm.sup.2, between about 3,000 cm.sup.2 and about 5,000 cm.sup.2, between about 4,000 cm.sup.2 and about 5,000 cm.sup.2, between about 2,000 cm.sup.2 and about 6,000 cm.sup.2, between about 3,000 cm.sup.2 and about 6,000 cm.sup.2, between about 4,000 cm.sup.2 and about 6,000 cm.sup.2, between about 5,000 cm.sup.2 and about 6,000 cm.sup.2, or ranges included therein.

[0037] In some embodiments, high doses of UV illumination are directed to an area on the skin that is less than about 6,000 cm.sup.2, less than about 5,000 cm.sup.2, less than about 4,000 cm.sup.2, less than about 3,000 cm.sup.2, less than about 2,000 cm.sup.2, less than about 1,800 cm.sup.2, less than about 1,600 cm.sup.2, less than about 1,400 cm.sup.2, less than about 1,200 cm.sup.2, less than about 1,000 cm.sup.2, less than about 800 cm.sup.2, less than about 600 cm.sup.2, less than about 500 cm.sup.2, less than about 400 cm.sup.2, less than about 300 cm.sup.2, less than about 200 cm.sup.2, less than about 100 cm.sup.2, less than about 50 cm.sup.2, less than about 25 cm.sup.2, or values therebetween.

[0038] In some embodiments, the high doses of UV illumination are directed to an area on the skin that is between about 1% BSA and about 30% BSA, between about 1% BSA and about 25% BSA, between about 1% BSA and about 20% BSA, between about 1% BSA and about 15% BSA, between about 1% BSA and about 10% BSA, between about 1% BSA and about 5% BSA, between about 3% BSA and about 30% BSA, between about 3% BSA and about 25% BSA, between about 3% BSA and about 20% BSA, between about 3% BSA and about 15% BSA, between about 3% BSA and about 10% BSA, between about 3% BSA and about 5% BSA, between about 10% BSA and about 30% BSA, between about 10% BSA and about 25% BSA, between about 10% BSA and about 20% BSA, between about 10% BSA and about 15% BSA, or ranges included therein. In some embodiments, the high doses of UV illumination are directed to an area on the skin that is less than about 30% BSA, less than about 25% BSA, less than about 20% BSA, less than about 15% BSA, less than about 10% BSA, less than about 5% BSA, less than about 3% BSA, less than about 1% BSA, or values therebetween.

[0039] Although the description above and accompanying drawings contains much specificity, the details provided should not be construed as limiting the scope of the embodiments, but merely as describing some of the features of the embodiments. The description and figures should not to be taken as restrictive and are understood as broad and general teachings in accordance with the present invention. While the embodiments have been described using specific terms, such description is for illustrative purposes only, and it is to be understood that modifications and variations to such embodiments, including, but not limited to, the substitutions of equivalent features and terminology may be readily apparent to those of skill in the art based upon this disclosure without departing from the spirit and scope of the invention.