Abstract:
Methods for treating erythematous papules by irradiating skin with light having a wavelength between about 525 nanometers and 550 nanometers are provided.

Description:
INTRODUCTION  
       [0001]     This patent application is a continuation-in-part of U.S. application Ser. No. 09/738,523 filed Dec. 15, 2000, which is herein incorporated by reference in its entirety. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The present invention relates in general to laser treatment of dermatological imperfections. The invention relates in particular to non-ablative laser treatment of erythematous papules such as acne and rosacea.  
       BACKGROUND OF THE INVENTION  
       [0003]     The aesthetic treatment of abnormal dermatological conditions such as acne and rosacea has hitherto involved using topical treatments, physical methods of pore extraction, and oral antibiotics as well as oral retinoids. Prior-art treatments and investigations of treatments have been concentrated primarily on the use of antibiotics, steroid therapies, and low intensity blue light for photochemical therapy. Treatment of dermatological imperfections such as acne and rosacea has received relatively little investigative attention. While such imperfections may not be considered as aesthetically unpleasant or inconvenient, they are nonetheless dermatological imperfections. There is need for a method of improving the character of these imperfections without causing damage to peripheral tissue, and without leaving an open wound that must subsequently heal. Such a treatment could produce a long-lasting effect by altering the dermal extracellular matrix surrounding the follicles, which are the sites where acne takes place.  
       SUMMARY OF THE INVENTION  
       [0004]     The present invention is directed to a method for treating erythematous papules as well as the skin between the papules. Acne-prone skin is erythematous not only in areas of active acne, but also in areas where acne has previously occurred, or where it is about to occur. In addition, acne lesions often have excess melanin pigment in the area where inflammation has caused deposition of excess epidermal melanin in the superficial dermis and in the area of the hair follicles. In one aspect, the method of the present invention comprises irradiating the skin to be treated with light (electromagnetic radiation) having a wavelength selected such that it is preferentially absorbed in a dermal region of the skin including a melanocyte layer of the epidermis and a region of superficial vasculature immediately below the melanocyte layer. The light is delivered at a fluence sufficient that the preferential absorption thereof stimulates a wound healing response in the dermal region without causing a wound. The wound healing response promotes growth of dermal collagen, and other extracellular matrix and inflammatory compounds, in the area surrounding the hair follicles. This reorganization of dermal collagen affects the structure and function of sebaceous glands, altering their activity and reducing the incidence, severity and appearance of erythematous papules such as, but not limited to, rosacea, and both inflammatory and comedonal acne.  
         [0005]     Preferably, the light has a wavelength between about 525 and 550 nanometers (nm). The light may be delivered in the form of pulses thereof or as a continuous beam swept or scanned over an area of skin being treated.  
         [0006]     In experimental treatments in accordance with the present invention, pulsed electromagnetic radiation having a wavelength of 532 nm, delivered by a frequency-doubled Nd:YAG laser was arranged to deliver a spot having a diameter of about 3 millimeters (mm). The pulse duration was about 2.0 milliseconds (ms). An average fluence of 7.5 Joules per square centimeter (J/cm 2 ) was used to treat 6 volunteer patients having active pustual, papular, and comedonal acne. There was on average a greater than 70% improvement in their acne following a series of three treatments administered a month apart. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]     The accompanying drawings, which are incorporated in and constitute a part of the specification, schematically illustrate a preferred embodiment of the present invention, and together with the general description given above and the detailed description of the preferred embodiment given below, serve to explain the principles of the invention.  
         [0008]      FIG. 1  schematically illustrates a section of human tissue including dermal layers and underlying vasculature thereof.  
         [0009]      FIG. 2  is a graph schematically illustrating absorptivity of hemoglobin and melanin as a function of wavelength in a wavelength region of the visible electromagnetic spectrum between 500 nanometers and 600 nanometers.  
         [0010]      FIG. 3  schematically illustrates laser apparatus used for experimental treatment of erythematous papules in accordance with the method of the present invention.  
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0011]     The method of the present invention relies on using laser radiation to stimulate the skin&#39;s wound healing responses. The laser radiation wavelength and the laser radiation fluence are selected such that the wound healing responses are stimulated without actually inflicting a wound. The wound healing responses promote growth or production of dermal collagen. The term “wound” here is meant to define an open wound, blister or any other effect which would be manifest in, or lead to, necrosis of tissue.  
         [0012]     The biology of wound healing is a very complex process. Cytokines released by the vascular endothelial cells and epidermal keratinocytes are responsible for initiating the increased production of collagen. This takes place in a series of interrelated steps via the resident cells of the dermis. These elements lie in the uppermost regions of the skin. By selecting a wavelength of laser radiation in a range between about 525 and 550 nm, the wound healing response is concentrated close to these upper regions of the skin, and accordingly close to the location of imperfections being treated.  
         [0013]     The dermis is composed of cellular and extracellular constituents that interact with one another to form a highly ordered, yet quite dynamic structure. Other than water, the major components of the extracellular matrix are collagen, elastic fibers, fibronectin, glycosaminoglycans, and proteoglycans. The stimulated growth and remodeling of dermal extracellular matrix “bulks-up” the dermal tissue, and alters the milleau surrounding the hair follicle and sebaceous glands. This alters the anatomy of the follicle and the sebaceous gland unit causing a reduction in comedonal, papular and pustular acne. The method may also be employed to treat other conditions that result in erythematous papules, such as rosacea. As such, the term erythematous papules is meant to include, but not be limited to, acne and rosacea.  
         [0014]     The superficial vascular endothelium and the epidermal keratinocytes are stimulated by heating them with light that is well absorbed by both structures. This requires that the light be optimally absorbed in both melanin and in hemoglobin of the superficial vasculature.  
         [0015]      FIG. 1  schematically illustrates a section of human skin including a region  10  generally defined as the epidermis and a region  12  generally defined as the dermis. The epidermis  10  includes an outer layer (stratum corneium)  14 , and a lower (melanocyte) layer  16  including melanin pigment. Some keratinocytes are heavily pigmented and contain melanosomes which feed melanin to the surrounding cells. The epidermis is made up primarily of keratinocytes.  
         [0016]     In the papillary, or upper dermis  12 , vasculature  18  has a superficial portion thereof comprising a plurality of capillary loops  20 . In the method of the present invention, absorption by melanin in melanocyte layer  16  and in capillary loops  20  of vasculature  18  preferentially heats a shallow region  20  immediately below layer  16  thereby heating the layer by conduction and providing the desired wound healing stimulus. It is believed, without being limited to a particular theory, that heating of keratincytes and the walls of the vessels of vasculature  18 , in particular of the capillary loops  20  close to the epidermis  10 , induces the secretion of cytokines that stimulate cells of the dermis  12  to produce the extracellular matrix and inflammatory compounds, in the area surrounding a hair follicle  24 . This reorganization of dermal collagen affects the structure and function of sebaceous gland  26 , altering their activity and reducing the incidence, severity and appearance of erythematous papules.  
         [0017]      FIG. 2  graphically, schematically illustrates absorptivity of blood (curve A) and melanin (curve B) as a function of wavelength in a wavelength region between 500 nm and 600 nm in the visible electromagnetic spectrum. In the preferred wavelength region of 525 to 550 nanometers absorptivity in haemoglobin is at or near a peak while absorption in melanin is also at a high level. The high melansome absorptivity helps in maintaining the desired heating effect at the superficial level in skin being treated. By way of contrast, in the “yellow” wavelength region around 580 nm where dye lasers emit, melanosome absorptivity is significantly less than at 525 nm and approaches equality with hemoglobin absorptivity. This is one reason why dye lasers are preferred in prior-art treatment of vascular disorders and the like. In such treatments, absorption of radiation by melanin could cause undesirable side effects such as blistering of skin as well as preventing penetration of the radiation to the lower lying vasculature where it is needed.  
         [0018]     In the inventive erythematous papule treatment method, electromagnetic radiation (light) preferably having a wavelength between about 525 and 550 nm, and having an appropriate pulse duration and intensity, is used to provide a selective, localized temperature increase in the superficial vasculature  20  and, intentionally and therapeutically, in melanocyte layer  16 . The temperature rise should be sufficient to stimulate the release of cytokines and other growth factors without appreciably damaging any of the structures of the skin. Preferably, this temperature is less than about 70° C., but must, of course, be higher than normal body temperature. It is believed that at wavelengths increasingly shorter than 525 nm, as absorption becomes increasingly, proportionately higher in melanin than in hemoglobin, that sufficient heating of the target region cannot be obtained without overheating the melanocyte layer and causing blistering. At wavelengths increasingly longer than 550 nm, decreasing melanin absorption will allow penetration of radiation to depths in the vasculature at which it is less therapeutically effective, if at all.  
         [0019]     The treatment radiation is preferably delivered by a laser. One suitable laser for providing radiation in the inventive treatment of erythematous papules is a frequency doubled Nd:YAG laser. Such a laser operates most efficiently by generating 1064 nm fundamental radiation and converting this radiation to 532 nm radiation by intracavity frequency doubling.  
         [0020]     Referring now to  FIG. 3 , laser apparatus  30  used for experimental treatments in accordance with the present invention includes a Coherent VersaPulseV intracavity frequency-doubled Nd:YAG laser  32  including a touch screen control display  34  for controlling operating parameters of the laser. Laser  32  delivers 532 nm radiation via a fiber-optic cable  36  to a handpiece  38 . Handpiece  38  includes optics (not shown) which allow delivery of the 532 nm laser radiation focussed in a range of spot sizes. Spot sizes are selectively adjustable by rotating a control ring  40 . A stand-off probe  42  attached to handpiece  38  contacts tissue  44  being treated to ensure that radiation is always delivered in the same spot size as the handpiece is moved to different locations on tissue  44 . It is also possible to employ a handpiece that delivers a collimated beam. This allows for a range of variation of working distance while still maintaining a selected beam size.  
         [0021]     In experimental treatments in accordance with the present invention, laser  22  was arranged to deliver a spot having a diameter of about 3 mm. The pulse duration was about 2.0 ms. An average fluence of 7.5 J/cm 2  was used to treat active acne lesions of volunteer patients. A total of 6 volunteer patients were treated.  
         [0022]     Active acne lesions having a size larger that 3.0 mm were treated by applying single pulses at adjacent locations over the area without overlapping pulses. There was a high degree of patient satisfaction with the improvement of their appearance after only two treatments (one treatment per month). There was on average a greater than 70% improvement in the acne after three laser treatments. The judgement of improvement was made by the patients themselves.  
         [0023]     In establishing a suitable fluence for treatment for each patient, test pulses were delivered to a selected test are of that patient&#39;s skin, in a range of increasing fluences, until a fluence level was reached which produced observable inflammation. Each test pulse was fired on a different portion of the patient&#39;s skin. It was found that fluences higher than 12 J/cm 2  at a pulse length of 2 ms generally caused blistering, even on light-skinned patients. Accordingly, a fluence less than about 10 J/cm 2  in a pulse having a duration of about 2 ms or generally less than 10 ms is preferred. It should be noted here that this simple inflammation does not constitute a wound as that term is defined herein. Under no circumstances should the fluence be sufficient to cause coagulation of blood in the vasculature.  
         [0024]     Inflammation is a very specific process and is not synonymous with irritation. It is emphasized, however, that it is not necessarily the inflammation in itself that is responsible for the dermal extracellular matrix deposition and corresponding improvements of the inventive treatment. Numerous inflammatory skin conditions, such as vasculitis, Sweet&#39;s syndrome and insect bites, occur without deposition of dermal extracellular matrix.  
         [0025]     The experimental treatments were performed without resort to any skin cooling mechanisms such as contact cooling, cryogen spray cooling or the application of cooling gels to areas being treated. It is possible, however, that the method of the present invention may be made part of an integrated approach to the treatment of erythematous papules by combining the above-described radiation therapy with application of agents such as alpha-hydroxy acids, retinoids and growth factors that can positively impact the healing response.  
         [0026]     It should be noted, here, that the while above-described experimental treatments were conducted using the 532 nm wavelength of a frequency-doubled Nd:YAG this particular wavelength should not be construed as limiting the invention. By way of example using an appropriately wavelength selective resonator, a frequency doubled Nd:YAG laser can be arranged to deliver other wavelengths in the region between about 525 nm and 555 nm. These other wavelengths are about 531 nm, about 537 nm and about 539 nm which can be produced by frequency doubling fundamentally radiation at respectively about 1061 nm, about 1073 nm and about 1078 nm, the term about here meaning that the wavelengths are stated as rounded to the nearest nanometer. 532 nm radiation may also be generated by a frequency-doubled Nd:YVO4 laser. The use of any other laser providing radiation in the preferred, 525 nm to 550 nm range is not precluded in the present invention, nor is the use of any source of non-coherent light delivering radiation in this preferred wavelength range. It should also be noted that while single pulse delivery of radiation in experimental treatments is described, it is also possible to use continuous wave (CW) radiation and scan the radiation over tissue being treated. Scan speed (accordingly the dwell time of a beam in a particular area) can be selected, consistent with the beam size and power in the CW beam, such that the dwell time of radiation at a point being treated (due to the time taken for a beam of finite size to pass that point) delivers the appropriate fluence as indicated above.  
         [0027]     The present invention is described above in terms of a preferred and other embodiments. The invention is not limited, however, by the embodiments described and depicted herein. Rather, the invention is limited only by the claims appended hereto.