What Is the Consensus Regarding the Efficacy of Phototherapy for Acne?

Acne affects 95 - 100% of adolescent boys and 83 - 85% of adolescent girls. Acne usually resolves before the age of 25 years. About 12% of women and 5% of men have acne at the age of 25 years. At 40 years of age, 1% of men and 5% of women have acne. Acne can manifest in adulthood either for the first time or as a recurrence in individuals who have had acne as an adolescent. Acne can lead to low self-esteem, loss of confidence and depression. It can even affect productivity and employability, and quality of life scales have assessed the impact of acne as similar to epilepsy or asthma. Scarring of the skin is also common and is difficult to treat.  

What Is Acne?

Acne is the result of blocked skin follicles. Excess oil (sebum) produced by the sebaceous glands in the hair follicle and accumulated dead skin cells obstruct the skin pore. The plugged follicle then becomes an ideal environment for bacterial proliferation. Propionibacterium acnes, a normal component of human skin flora, grows in the lipid-rich (fatty) microenvironment of the hair follicle. In acne vulgaris, Propionibacterieum acnes (P. acnes) produces inflammatory products that result in acne lesions. 

Acne is considered a polymorphic disease (that is, it presents in multiple forms) and two patterns of disease can usually be noted. In non-inflammatory acne, often seen in the peri-pubertal age group (8-16), increased sebum production in the face, chest, back and shoulders results in the formation of blackheads or open comedones. In some instances, appearance of whiteheads or closed comedones can occur, heralding the progression to inflammatory disease.

The inflammatory disease associated with acne is characterised by the presence of blackheads, whiteheads, papules and pustules. Cystic nodules and scarring can also be present. Redness and seborrhoea (greasy skin due to excess secretion of sebum) can also occur.

The presence of acne may persist over years. Nodules may become more painful and an increased risk of scarring is present. Following the inflammatory phase, red or hyperpigmented changes can occur, which can last several months or even years.

On the upper chest and shoulders, hypertrophic or keloid scarring (a type of fibrous scar) may develop. Atrophic or “ice-pick” scars may usually develop on the face. In addition, small depressions and slight discolouration can develop and last for up to 12 months.

How Is Acne Treated?

The treatment of acne is based upon its severity (mild, moderate, severe) and the type(s) of lesion(s) present (noninflammatory, inflammatory, mixed). In general, the treatment of mild acne involves the use of topical agents, whereas the treatment of moderate and severe acne usually involves the use of both topical and systemic therapies or systemic therapy alone. 

How Does Phototherapy Work?

The use of light therapy in medicine has a long history. Although phototherapy had no scientific basis at the time, natural sunlight was used for medical treatments in ancient Egypt and Greece. Later, Roman and Arab physicians introduced light therapy into general medical use. Sir Isaac Newton discovered the visible spectrum of light in 1672, with ultraviolet light identified in the early 1700s. The entire electromagnetic spectrum is made up of ultraviolet, visible light, and infrared. The human eye can only see the ‘visible light’ sector of the spectrum. This excludes ultraviolet and infrared wave energy which are not ‘visible.’ The first discovery of electromagnetic radiation other than visible light came in 1800, when William Herschel discovered infrared radiation. The light spectrum was first used as a medical treatment in 1893 by Niels Ryberg Finsen who determined that lengthy exposure of smallpox sufferers to red light accelerated the healing of pox lesions and prevented the formation of pockmarks. Finsen was awarded the Nobel Prize for his work in phototherapy.

Over the next century, many uses were identified for phototherapy, ranging from skin disorders to psychiatric illnesses:

• jaundice in newborns (yellowing of skin in babies)
• severe plaque psoriasis (flaky, itchy skin disease)
• seasonal affective disorder (SAD)
• atopic dermatitis (itchy skin disorder)
• vitiligo (loss of color in skin)
• urticaria (hives)
• pruritus (itchy skin)

Phototherapy is the use of bright light sources with a specific wavelength or range of wavelengths for a specified amount of time to treat various medical conditions. For example, psoriasis and vitiligo are commonly treated with ultraviolet light while seasonal affective disorder utilises white light (a combination of all visible light) emitted from a ‘light box.’  Different wavelengths of light produce varying effects on the human skin.

Although antibacterials and retinoids are still the mainstay of treatment for acne, their success rate varies.

Acne often improves after exposure to sunlight, and this observation has led to the development of laser and other light therapies. In general, light therapy treatments for acne vulgaris target P. acnes bacterial levels and/or disrupt the sebaceous glands, and may also have anti-inflammatory effects via action on inflammatory cytokines.

Blue light therapy

P. acnes produces molecules called porphyrins. Excitation of porphyrins with blue light (390-420 nm) causes them to release free radicals into the bacterium itself, thus killing the bacteria. Visible light can destroy propionibacteria by exciting bacterial porphyrins (protoporphyrin IX, coproprophyrin III) leading to the formation of toxic oxygen radicals. The absorption maximum of bacterial porphyrins is in the range of 400–420 nm (violet and blue light). Further, smaller absorption peaks exist in the green, yellow and red spectral ranges. Infrared lasers, radiofrequency devices and low-energy pulsed dye lasers are thought to improve acne by thermally damaging sebaceous glands directly.

Intense pulsed light (IPL) therapy

This is a form of phototherapy which releases a rapid series of short pulses of yellow, green and red light. The yellow and the green lights destroy the bacteria that cause acne, and the red light targets the sebaceous glands, causing the inflamed, overactive glands to shrink. The heating caused by the red light also stimulates the production of collagen, which aids in healing and improves skin tone. The rapid pulsing prevents overheating of skin, thermal damage and discomfort of the patient. Most patients experience no side effects from IPL treatment, but in rare cases, there can be skin discoloration in treated areas, the skin becoming either lighter or darker. Hair loss can occur in treated areas and can be permanent. Small blisters can appear as a side effect of IPL sessions as well. IPL treatments are not recommended for individuals with very dark skin or who are very tanned, and treatment has not been proven safe for pregnant women.

Photodynamic therapy (PDT)

Another form of phototherapy which uses light-activated creams applied to skin. PDT is a simple biochemical process that requires three basic things in order for the reaction to take place. These include a photosensitiser, an appropriate light source, and molecular oxygen.

The most common photosensitiser used in dermatology today is aminolevulinic acid (ALA). In dermatologic PDT, a 20% 5-ALA solution or its methyl ester cream (MAL) are the most common photosensitisers utilised. ALA is known commercially as Levulan® Kerastick. The trade name for MAL is Metvix, except in the United States, where it is called Metvixia.

ALA and MAL are selectively absorbed in the skin by actinically damaged skin cells, nonmelanoma skin cancer cells, and the pilosebaceous unit. It is because of this selectivity that both ALA and MAL are used to treat actinic keratoses and in photorejuvenation of the skin.

PDT essentially has three steps:

• First, a light-sensitising liquid is applied to the skin.
• Second, there is an incubation period ranging from 30 minutes to 4 hours.
• Finally, the target tissue is exposed to a specific wavelength of light (e.g. blue light or pulsed dye laser) that then ‘activates’ the photosensitising medication.

Any light source, either laser or nonlaser, with a high output at an absorption maximum of the photosensitiser can be used for photodynamic therapy (PDT). ALA can be ‘activated’ using blue light sources, potassium titanyl phosphate (KTP) lasers, pulsed dye lasers (PDL), and intense pulsed light (IPL) sources.

The only FDA-approved indication for ALA photodynamic therapy (PDT) and MAL photodynamic therapy in dermatology is currently the treatment of actinic keratosis. Common off-label uses, however, include the treatment of basal cell carcinoma, photoaging, and acne vulgaris. PDT tends to be more painful than light alone, and more likely to produce erythema (redness), oedema (swelling), initial worsening of acne, crusting and epithelial exfoliation (surface skin shedding). The severity of side effects depends partly on skin type, as melanocytes absorb more light due to their pigment. The ALA-PDT combination can destroy the P. acnes bacteria that trigger acne and appears to enhance the overall texture of skin by promoting the normal sloughing off of dead keratinised skin cells within pores and follicles.

The consensus regarding the efficacy of Phototherapy for Acne?

According to reviewed evidence, blue light monotherapy reduces the counts of inflammatory lesions by 36–62.5% and can be considered for the treatment of mild-to-moderate papulopustular acne, whereas the evidence regarding the efficacy of red light compared with placebo is still conflicting. The FDA has approved the use of high-intensity, narrow-band blue light to treat mild to moderate acne. This pain-free light is safe and uses no ultraviolet (UV) light or lasers.

Red light phototherapy is less effective for the eradication of P. acnes than blue light phototherapy, but efficacy of red light phototherapy can be markedly enhanced by the addition of 5-aminolevulinic acid (ALA). Narrowband light therapies are typically well tolerated and conveniently administered; but their mode of action, primarily against P. acnes, requires repeated application, which argues for its use in combination with other medical treatments with anticomedogenic and comedolytic effects. Visible light as monotherapy is not recommended for the treatment of comedonal, severe papulopustular and conglobate acne.

Although PDT is effective in the treatment of severe papulopustular/moderate nodular acne, it cannot yet be recommended due to a lack of standard treatment regimens that ensure a favorable profile of acute adverse reaction, including pain, erythema, severe folliculitis and desquamation. Furthermore, destruction of pilosebaceous units and scarring have been reported after selective phototermolysis (Indocyanine green and diode laser) treatment for acne, raising concerns about the long-term effects of PDT with regard to the maintenance of endocrine and immunological functions of sebaceous glands.

According to an article reviewing PDT practicability, a topical short-contact (90 min or less) ALA or MAL using a noncoherent light source at 2- to 4-week intervals for a total of two to four treatments produces the greatest clinical effect and shows a good side-effect profile, resulting in acne remission for at least 3 months up to a year. Indocyanine green and indole-3-acetic acid are new photosensitizers with comparable efficacy in mild-to-moderate acne vulgaris, which reduce mainly inflammatory and, to a lesser extent, noninflammatory lesions and sebum secretion. 

The major disadvantage of PDT is that many participants experience side effects severe enough for them to discontinue treatment. Patients find the treatments painful, and afterwards most developed erythema, then severe folliculitis, followed by desquamation. The side effects are often severe enough for participants to stay off work or school. Nonetheless, in those trials that did assess patient satisfaction scores for PDT, most patients felt their acne had improved significantly. Dermatologists do report cases of patients who have had clear skin for years following PDT.

Additional concerns exist about the long-term effects of PDT. In one study, biopsies of the skin treated with PDT showed that the targeted pilosebaceous units had been 'largely destroyed.' As other authors have suggested, the pilosebaceous units play an important role in the immune system of the skin, and thus, this technique could pose long-term risks. For dermatological purposes, PDT is only FDA-approved for actinic keratosis (a type of scaly skin lesion), but many dermatologists already use ALA- and MLA-based compounds as "off label" acne treatments. PDT is approved by the U.S. Food and Drug Administration (FDA) only for the treatment of actinic keratosis. Its off-label application in the treatment of acne was first reported in two studies in 2000, and numerous studies investigating different aspects of the treatment have been published since then.

While some clinicians have embraced its use, PDT faces a number of challenges to becoming a mainstream acne treatment, in addition to its lack of FDA approval, the lack of consensus on optimal treatment parameters and methodology and severe side effects resulting in patient compliance issues raises significant concerns about its benefit/risk profile.

Finally, the sun, sun lamps and tanning booths should not be used to treat acne because none have been proven effective and all expose the skin to harmful ultraviolet (UV) light. Exposure to UV light increases the risk of developing melanoma and other types of skin cancer.

How Effective is Laser Therapy for acne?

Laser therapy or laser phototherapy is a method where light from a laser is applied to tissue in order to influence cell or tissue functions with such low light intensity that heating is negligible.

The effects achieved are hence not due to heating but to photochemical or photobiologic reactions like the effect of light in plants. The lasers used are normally called therapeutic lasers or medical lasers.

Different types of lasers are used for acne treatment, and they work in different ways. The mechanism of action of different lasers is not completely understood at present.

Systems that emit energy in the visible spectrum such as dye lasers and the potassium-titanyl-phosphate (KTP) laser might have antimicrobial effects by exciting bacterial porphyrins. Lasers working in the infrared range might act in both in an anti-inflammatory manner and also by causing thermal damage to the sebaceous glands.

Pulsed dye laser

In a randomised, controlled, double-blind study, 12 weeks after a single application of a pulsed dye laser (585 nm) a significantly greater reduction of inflammatory lesions (49 %) was observed in comparison to a control group receiving sham (placebo) therapy (10%).30 Further publications report moderate to good 32 therapeutic effects on acne by the dye laser.

Diode laser

In a randomized, blinded and intra-individually controlled study 33 on 27 patients with acne on the back a diode laser (1450 nm, 14–22 J/cm2) was used in combination with a cryogen spray with the intention of thermally damaging sebaceous glands in deeper cutaneous layers and simultaneously protecting the epidermis from thermal damage by cooling. Four treatments at intervals of 3 weeks were performed. The back areas treated with laser/cryogen demonstrated a distinct reduction of acne lesions up to 6 months after the end of treatment (98 %) in comparison to the control areas treated only with cryogen spray (5 %). Short-term side effects were erythema, edema and transient hyperpigmentation. A follow-up study confirmed the therapeutic potential of the diode laser on the face. Here, too, 4 treatments at 3 week intervals were performed. Twelve weeks after the end of therapy, a 61% reduction in the number of acne lesions was noted from baseline. According to existing studies, the diode laser (1450 nm) appears to possess therapeutic potential for active acne.

Erbium-glass lasers

A carefully documented observational study found the Erbium: Glass laser (1540 nm, 60 J/cm2) to be effective in patients with moderate to severe facial acne. Four treatments at intervals of 2 weeks were performed. Six months after the end of treatment a reduction of acne lesions by 78 % was registered.  Another study on 25 patients with mild to moderate acne with the Erbium: Glass laser (1540 nm, 40 J/cm2), 4 treatments in 4 week intervals resulted in a distinct reduction of acne lesions already after the first treatment and a reduction by 71 % after 6 months, by 79 % after one year and still by 73 % after 2 years. On the basis of interesting pilot studies further trials on the efficacy of the Erbium:Glass laser are desirable.

Nd:YAG laser

The Nd:YAG laser (1320 nm), working in the infrared range, was used to treat 46 patients with facial acne in a randomised, single-blind half-side comparison trial. Three non-ablative treatments were performed at an interval of one week. Seven weeks after the end of treatment the treated half of the face showed a slight reduction of open comedones, but no reduction of closed comedones or inflammatory lesions. According to present data, the Nd:YAG laser (1320 nm) is not suitable for the treatment of active acne.

KTP lasers

In a randomized, unblinded half-side comparison the KTP laser (532 nm) was employed for the treatment of patients (n = 26) with moderate acne. Four treatments within 2 weeks were performed. One week after the end of treatment a reduction of acne severity by 34.9 % was seen, after 4 weeks only 20.7 %. Significant side effects were not observed. The KTP laser cannot be recommended for the treatment of acne at present based on one study despite the report of moderate improvement.

Radiofrequency

Long-wave radiofrequency is used in aesthetic medicine for rejuvenation. No controlled studies its on use for active acne exist.

How Is Acne Scarring Treated?

Among the therapeutic tools for treatment of acne scarring are resurfacing methods (these procedures remove the outer layers of skin), fillers, and other dermal remodeling techniques. These methods can be adapted to treat specific scar types. Resurfacing is performed with lasers, chemical peels, dermabrasion, or platelet-rich plasma. Resurfacing can be ablative, partially ablative or nonablative.

Ablative resurfacing entails removal of the epidermis and partial thickness dermis, and is considered by most as the gold standard for pitted scars and some box-car scars. While ablative resurfacing is most effective if it is deep, thereby removing as much as possible of the depressed scar, it cannot be so deep as to destroy the base of the hair follicles; such destruction could impede skin regrowth, and induce scar formation at the treated site.

Carbon dioxide resurfacing is the most effective but also most operator-dependent method for deep ablative resurfacing. 

Dermabrasion is possibly even more effective, but this is another procedure that is very technique dependent.

Definitive ablative resurfacing results in 2 weeks of patient downtime, during which period re-epithelialization occurs. 

Treating acne with lasers has limitations. Although topical anesthetics are used for the procedures, laser treatment can be painful. Laser treatment can cause redness that persists for months, though it normally subsides within a week. Lasers and other light treatments do not work for everyone. Right now, there is no way to know who will see clearer skin and how much the skin will improve with a laser therapy. Even if other treatments do not work, laser treatment may not be appropriate for people with certain skin conditions, such as psoriasis, cystic acne or extremely dry skin.

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