ACNE SCAR LASER TREATMENT

Additional and scientific information on how laser treatment for acne scar works and before and after treatment results

HOW DOES ACNE SCAR LASER TREATMENT WORK AND WHAT ARE THE RESULTS?

Throughout human history, acne has been a scourge, and, although not usually life-threatening, has physically and emotionally scarred millions. Traditional treatment for active acne has revolved around cleansers, topical agents and oral antibiotics, with the more recent addition of retinoids, both topical and systemic. Acne scarring, formerly treated with excision and dermabrasion, has benefitted from newer alternatives, such as fillers and non-ablative laser treatments. Traditionally, physicians and surgeons have postponed treatment for acne scarring until the active acne has subsided, perfectly sensible in the days when invasive open procedures were the mainstay of treatment.

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Although every teenager has noticed that acne usually improves when exposed to sunlight, light-based therapy for active acne was first reported just a year or two ago, based on the observation of improvement during non-ablative laser treatment for acne scarring. Since then, there's been a flurry of case reports, anecdotal evidence, and approvals of various lasers and light-based devices for the treatment of active acne, pustules, comedones, etc. Although Laser and other light-based treatments for active acne appear to be very effective, their exact place in the spectrum of treatment options for this condition has yet to be scientifically validated!.

Acne is an inflammatory disease of the pilosebaceous unit. Obstruction of the duct of the sebaceous gland, usually caused by abnormal maturation of cells in the duct, leads to an inflammatory reaction the various oils, or lipids in the obstructed gland. Subsequent infection of the inflamed, dilated follicles by Proprionbacterium Acnes (P. Acnes), a common skin bacterium, can lead to superficial or deep scarring. Factors which affect maturation of the cells in the sebaceous gland and duct include hormones (especially androgens), excess sebum production, and inflammatory mediators produced not only by the body, but by the P. Acnes bacteria themselves. The goal of acne treatment is to decrease the number of bacteria, eliminate obstruction of the duct of the sebaceous gland, and "optimize" the quality and quantity of sebum prodcution.

Porphyrins are ring-like molecules found universally in living organisms (hemoglobin and chlorophyll both contain porphyrin rings). Certain porphyrins, when exposed to light in the presence of oxygen, can act as a photosensitizer by absorbing light energy and transferring it to oxygen molecules, creating highly reactive Singlet Oxygen, which is capable of damaging nearby cellular structures including cell membranes, proteins, and DNA. Porphyrins can be either naturally formed inside a "target" tissue (such as a bacterial cell), or somehow administered so that they're concentrated in the target tissue, as in photodynamic therapy. The light energy used to activate the photosensitizer should be at a wavelength well absorbed by the porphyrin.

Absorption spectrum for porphyrins. Note the absorption peaks in the visible spectrum, and the various light sources that generate light at those wavelengths

A variety of light sources can be used for the treatment of Acne. Two mechanisms of actions have been proposed:

Direct absorption of visible light energy by porphyrins normally found within P. Acnes bacteria. Light energy is absorbed by bacterial porphyrins, triggering production of toxic singlet oxygen which damages or destroys the bacteria (this is probably why a day at the beach sometimes improves acne). Almost any visible light source can be used, including narrow-band light sources such as the ClearLight (Lumenis) and Blu-U (DUSA) (415-420nm), assorted IPL devices (broadband light) copper vapor lasers (510nm), KTP lasers (532nm), pulse dye lasers (585-595nm), and various orange/red light lasers or light sources (GentleWaves, etc) 610-635nm. Note that all of these light sources have wavelengths corresponding to an absorption peak of porphyrins, in this specific instance, P. Acnes coproporphyrin. Longer wavelengths have the advantage of penetrating deeper in to the skin, but do not activate porphyrin as well.
Thermal injury to the sebaceous glands using Near InfraRed (NIR) lasers such as the CoolTouch (1320nm), SmoothBeam (1450nm), Aramis (1540nm), monopolar adiofrequency devices such as the ThermaCool TC (Thermage), or combination devices such as the or Syneron Aurora/Polaris (bipolar RF with 940nm diode laser). In each instance, dermal heating disrupts the sebaceous glands while sparing the epidermis, while involution of the glands induces a long-term remission of the acne.

The prinicpal advantage of laser and light-based treatment of acne is safety. At least in theory, the risks of prolonged antibiotic use and retinoid therapy can be avoided, as well as the expense and inconvenience of prolonged topical treatments, acne medications, creams, gels, etc. Whether or not laser treatments should be used as first-line treatment for acne, or even for prevention of acne, remains unclear at this time.

In our experience, 80% of patients with moderate to severe facial acne will respond to a single treatment with the 585nm pulse dye laser or the 1320nm Nd:YAG laser. Usually a response will be apparent in less than 2 weeks, and last at least several months. Patients may have an additional treatment 2-4 weeks later if needed, and repeat treatments later on. We stress that treatment protocols are empiric, and have not been scientifically validated!

This patient with severe cystic acne was treated with daily topical AHA and 3 pulsed dye laser (2J @ 1.5 msec 13mm spot size) treatments spaced 3 weeks apart. Pretreatment (left), 4 months post treatment (right).

Photodynamic therapy (PDT) for Acne: Photodynamic therapy (PDT) is the application of a photosensitizing medication, which is then stimulated by light in the presence of molecular oxygen, to obtain a therapeutic result. Although PDT has been used for over 40 years, problems with persisent photosensitization and marginal light delivery systems have limited it's use. During the last few years, the availability of effective topical photosensitizers and the simplicity of delivering light energy to the skin have made practical applications of PDT a reality.

Photosensitizers:To be an effective photosensitizer, a drug needs to be preferentially taken up by a target cell and absorb light energy, and transfer this energy to produce an active species capable of causing localized cell damage. Porphyrins, found almost every biologic system, are particularly suited to this task. Typically, porphyrins strongly absorb visible light, with an absorption peak in the 400nm (near UV) range, and smaller peaks in the visible spectrum to about 630nm (red). Because tissue absorption is wavelength-dependent, deeper tissues must be irradiated with longer wavelengths to get adequate absorption for a therapeutic effect, while shorter wavelengths may be used for more superfical applications, ie, skin.

Hematoporphyrin derivative, or HPD (Photophrin) was the first widely used photosensitizer. Delivered intravenously, it's relative lack of specificity, low absorption at the treatment wavelengths (typically 630nm), and persistence in tissue causing prolonged photosensitivity, limits its use as a therapeutic cutaneous photosensitizer. The ideal photosensitizer should be specifc for a given target tissue, have high absorption at deliverable wavelengths, efficiently create active oxygen species when excited, and clear rapidly after treatment.

5-ALA

PDT for acne "amplifies" the effect of light energy on P. Acnes bacteria and overactive sebaceous glands. 5-ALA (aminolevulinic acid, Levulan), a chemical precursor which occurs naturally in cells, is applied to the involved area on the skin. 5-ALA is preferentially absorbed by abnormal and/or metabolically active cells, where it's used to synthesize Protoporphyrin IX, which accumulates in the target cells. After an incubation period, the protoporphyrin-laden cells are stimulated by light energy, triggering the production of activated singlet oxygen, which in turn induces cell disruption and death in the target structures, in this case the sebaceous glands and bacteria.

Almost any light source that has a wavelength or wavelengths corresponding to an absorbption peak of porphyrin may be used to excite the photosensitizer.

ALA and porphyrin synthesis: 5-aminolevulinic acid occurs naturally in cells, and is the prinicpal precursor in the porphyrin synthesis pathway. Metabolically active cells rapidly convert ALA to porphyrin, particularly protoporphyrin IX, to which a ferrous ion is added to form heme. When applied topically to skin, ALA is concentrated in sebaceous glands, hair follicles, and to a lesser extent, epidermal cells. Other metabolically active cells such as those in Actinic keratoses and cutaneous neoplasms will also take up ALA and synthesize protoporphyrin IX, which will accumulate after stores of intracellular iron are depleted. Studies using fluorescence microscopy demonstrate higher concentrations of Protoporphyrin IX in acne lesions and actinic keratoses than normal surrounding skin. P. Acnes bacteria otherwise present in follicles and acne lesions also take up exogenous ALA to form Protoporphyrin IX and Coproporhyrin, thus enhancing the effect of light energy on the bacteria.

The prinicpal advantage of PhotoDynamice and Laser/Light based treatment of acne is safety. At least in theory, the risks of prolonged antibiotic use and retinoid therapy can be avoided, as well as the expense and inconvenience of prolonged topical treatments, acne medications, creams, gels, etc. Whether or not lPDT/laser/light source treatments should be used as first-line treatment for acne, or even for prevention of acne, remains unclear at this time.

Immed response erythema, scaling, see P.6

Ancillary benefit in older patients re: aks, hyperpigmentation, pore reduction, fine lines

role in tx acne: unclear, seems to have excellent safety profile, less problems oral meds, esp. accutane.

Notes on Singlet Oxygen: Each oxygen atom has 8 electrons, 2 in the 1s orbital, 2 in the 2s orbital and 4 in the 2p orbitals ( 1s2/2s2/2p4). To form O2, each Oxygen atom shares 2 electrons to form a double covalent bond. In Oxygen's most stable configuration, triplet oxygen, the two outermost electrons exist each in their own orbital with parallel (unpaired) spins, making molecular oxygen O2 a free radical, or rather, a diradical. This property is what makes molecular oxygen so effective as a terminal electron recipient in cellular respiration (oxidative phosphorylation). The term triplet refers to a state in which an electron pair in a molecule has spins that are parallel, or unpaired, which will yield a triple peak on Electron Spin Resonance spectroscopy (ESR).

Addition of energy to triplet O2, either directly from a UV photon or by transfer from a pigment molecule, will flip the spin of an electron, causing it to pair with the other in a single outermost orbital, leaving a vacant orbital. This configuration yields a single peak on ESR, hence the name singlet Oxygen. As energetic as singlet oxygen may be, strictly speaking it is not a true free radical.

The vacant orbital will eagerly accept two more electrons. Addition of another electron to the outermost orbital yields a superoxide ion, and one more will yield a peroxide ion. These molecules remain highly reactive and will reduce almost any molecule in a biologic system by shedding the extra electrons (as in lipid peroxidation), or they may accept a proton to yield H2O (from superoxide) or H2O2 (from peroxide).

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