Among the Q bands in the PPIX absorption spectrum, a peak at 575 nm is amenable to activation through PDL [21]. PDL (585 nm) following topical 20% ALA was used for the treatment of AK, but with purpura and crusting (see Photoaging) [22]. LP PDL (595 nm) following short incubation ALA was shown to be safe and effective for AK with minimal and rapidly resolving side effects [23]. The advantages of this light source included variable pulse duration in the nonpurpuric range; a longer wavelength with greater penetration depth as compared to blue light; dynamic cooling spray to minimize discomfort; large 10 mm spot size, and great rapidity of treatment with a firing speed of 1 Hz [23]. By targeting hemoglobin, the additional advantage of minimizing erythema within acne lesions or scars is also proffered by this light source.
A reduction in sebaceous hyperplasia was observed following ALA and LP PDL, a finding which was subsequently reproduced [24,25]. On the basis of these findings, topical ALA followed by LP PDL and PDL was assessed in a pilot study of acne patients employing a single treatment with 1-month follow-up [24]. The patient mean percent clearance rates of acne lesions following a single treatment were 69% for the LP PDL and 59% for the PDL [23]. The side effects were minimal, involving mild erythema lasting for 1-2 days.
Topical short incubation (1 hour) ALA followed by LP PDL (595 nm) combined with topical therapy was assessed in a 19-patient study of the treatment of recalcitrant acne of various types and levels of severity [4]. The study patients had failed conventional therapies, including isotretinoin, and exhibited mild-to-severe comedonal, inflammatory, and cystic acne. The mean percent lesional clearance rate per treatment for the LP PDL PDT group was 77%, while all patients including control groups were maintained on topical therapy [4]. Complete clearance was achieved following a mean of 2.9 treatments (range 1-6) and maintained for a mean follow-up interval of 6.4 months (range 1-13). The side effects were minimal and consisted of mild erythema resolving within 1-2 days. Control patients maintained on topical therapy achieved lower rates of clearance: conventional medical therapies achieved 20%, and laser energy alone 32% [4]. The efficacy rate of ALA and LP PDL combined with topical therapy appears to be higher than other light sources used. Prior studies of ALA PDT employing blue and red light or lasers, or IPL demonstrated lesional clearance rates of 32-75% after multiple treatments [5,9,11,15-18], LP PDL PDT combined with topical therapy resulted in a mean lesional clearance rate of 77% per treatment, and was the first PDT regimen to achieve complete clearance for up to 13 months follow-up [4]. LP PDL PDT is performed at monthly intervals, which is more practical than more frequent intervals used in other protocols. A photographic example of a patient with recalcitrant, severe, cystic acne prior to and 14 months following 3 treatments with LP PDL PDT is shown in Fig. 21.1A and B, respectively, with dramatic long-term remission.
In the aforementioned study, LP PDL alone demonstrated efficacy when compared to conventional therapy [4]. The mean clearance rate of LP PDL alone was 32% per treatment
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(a) (b) Figure 21.1 Recalcitrant acne responds to LP PDL-mediated PDT. A patient prior to (A) and 14 months following three treatment sessions (B) of topical ALA 1-hour incubation and LP PDL at a fluence of 7.5 J/cm2, 10 ms pulse duration, 10 mm spot size, and DCD of 30 ms with 30 ms delay. Both the cystic lesions and active erythematous scars improved dramatically following treatment. This patient remained clear to 14 months follow up. |
as compared to 20% for the topical control, though the comparison was limited by sample size [4]. This efficacy of LP PDL may be fluence-dependent, as this report employed flu – ences of 7-7.5 J/cm2 [4]. An earlier study had suggested efficacy of PDL (585 nm) in treating acne vulgaris [26], though another group was unable to reproduce these findings when low fluences of 3 J/cm2 and short pulse durations of 350-550 ps were used [27]. It is possible that use of LP PDL at higher fluences and longer pulse durations augments photodynamic activation of porphyrins and photothermal effects on vascular targets, without exceeding the purpura threshold [1]. The mechanisms of acne clearance may also involve the targeting of blood vessels and a resultant antiinflammatory effect as described in the treatment of scars by PDL [28,29]. LP PDL may photoactivate endogenous porphyrins produced by P acnes in the sebaceous follicle, potentially inducing sebaceous gland shrinkage, and decreased bacterial counts as has been shown for blue and red light [1]. Histopathologic evaluation of LP PDL-treated acne lesions will be necessary to elucidate the biological mechanism of the observed clinical findings.
An advantage of the choice of LP PDL as a PDT light source in treating acne is a dramatic improvement in erythematous scars [4]. PDL and LP PDL have been shown to effectively treat active erythematous scars, hypertrophic scars and keloids in particular [28,30,31]. In addition, ALA accumulates in papillary blood vessels and may mediate photodynamic and photothermal injury to blood vessels [32]. PDT has been employed for the treatment of vascular malformations and port wine stains [33]. Lichen sclerosus et atrophicus, a scarring dermatosis with dilated blood vessels in the dermis, was successfully treated by LP PDL – mediated PDT with a 3-year disease – free follow-up [34]. Thus, enhanced resolution of erythematous acne scars may be achieved with ALA and LP PDL. A photographic example of an acne patient whose acne and erythematous acne scars improved from ALA and LP PDL is shown in Fig. 21.2A and B, with acne and scars at baseline and clearing following treatment to 1-year follow-up, respectively.
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(a) (b) Figure 21.2 Inflammatory acne and erythematous acne scarring treated with ALA and LP PDL. A patient prior to (A) and 1 year following (B) 5 monthly treatments with topical ALA 1-hour incubation and LP PDL at a fluence of 7.5 J/cm2, 10 ms pulse duration, 10 mm spot size, and DCD of 30 ms with 30 ms delay. This patient has been maintained on topical therapy without recurrence to 2 years’ follow up. |
Topical ALA has also been combined with IPL to treat moderate to severe acne [5]. In one study, IPL (430-1100 nm) following short (1 hour) incubation ALA yielded a response in 12 of 15 patients [5]. Once weekly treatments reduced acne counts by 50.1, 68.5, and 71.8% at the end of the final treatment, with 1-month, and 3-month follow-up without recurrence of treated lesions [5]. In an 18-patient study, ALA with blue light or combination of optical and radiofrequency energy, was evaluated [6]. In that report, ALA was incubated for 15-30 minutes, patients received two to four treatments over a 4-8-week period, and salicylic acid peels [6]. Among the 12 patients who responded, 11 were rated as a 50% response and 5 patients were rated a 75% response [6]. These reports suggest that short incubation ALA with activation by IPL may be an effective, well-tolerated acne treatment and larger, controlled studies are warranted. In addition, due to the photorejuvenative properties of IPL, this may be an approach for the adult acne patient.