Topical ALA-photodynamic therapy for the treatment of acne vulgaris.

Topical aminolevulinic acid is converted into a potent photosensitizer, protoporphyrin, in human hair follicles and sebaceous glands. Photodynamic therapy with topical aminolevulinic acid was tested for the treatment of acne vulgaris, in an open-label prospective human study. Each of 22 subjects with acne on the back was treated in four sites with aminolevulinic acid plus red light, aminolevulinic acid alone, light alone, and untreated control. Half of the subjects were treated once; half were treated four times. Twenty percent topical aminolevulinic acid was applied with 3 h occlusion, and 150 J per cm2 broad-band light (550-700 nm) was given. Sebum excretion rate and auto-fluorescence from follicular bacteria were measured before, and 2, 3, 10, and 20 wk after, treatment. Histologic changes and protoporphyrin synthesis in pilosebaceous units were observed from skin biopsies. Aminolevulinic acid plus red light caused a transient acne-like folliculitis. Sebum excretion was eliminated for several weeks, and decreased for 20 wk after photodynamic therapy; multiple treatments caused greater suppression of sebum. Bacterial porphyrin fluorescence was also suppressed by photodynamic therapy. On histology, sebaceous glands showed acute damage and were smaller 20 wk after photodynamic therapy. There was clinical and statistically significant clearance of inflammatory acne by aminolevulinic acid plus red light, for at least 20 wk after multiple treatments and 10 wk after a single treatment. Transient hyperpigmentation, superficial exfoliation, and crusting were observed, which cleared without scarring. Topical aminolevulinic acid plus red light is an effective treatment of acne vulgaris, associated with significant side-effects. Aminolevulinic acid plus red light causes phototoxicity to sebaceous follicles, prolonged suppression of sebaceous gland function, and apparent decrease in follicular bacteria after photodynamic therapy. Potentially, aminolevulinic acid plus red light may be useful for some patients with acne.

Time-sequence histologic imaging of laser-treated cherry angiomas with in vivo confocal microscopy.

OBJECTIVE: To chronicle the pathophysiologic changes that occur subsequent to laser treatment of vascular lesions, we used a confocal scanning laser microscope that yields high-resolution microscopic images of skin in vivo. METHODS: Cherry angiomas were treated with the 585-nm flashlamp-pumped pulsed-dye laser (PDL) and the 568-nm continuous-wave krypton laser. Repeated confocal reflectance imaging was performed before and immediately after treatment, as well as after several hours, 1 day, 2 days, 1 week, 2 weeks, 3 weeks, and 4 weeks. RESULTS: Before treatment, confocal images revealed dilated blood vessels ranging from 10 to 50 microm in caliber, closely spaced at 5 to 50 microm apart. After PDL treatment, amorphous cords of refractile material conformed to the shape of the original vessels, followed by dark nonrefractile spaces where the vessels once were. Inflammation and necrosis ensued, with eventual replacement after 3 weeks by normal-appearing skin. After krypton laser treatment, dark nonrefractile spaces appeared immediately, with subsequent inflammation, necrosis, and eventual healing by 4 weeks. CONCLUSION: Confocal laser microscopic imaging elucidates the dynamic pathophysiologic events that occur after laser treatment of vascular lesions and has added insight into the different mechanisms of vessel damage induced by the PDL and krypton laser.

Confocal laser microscopic imaging of actinic keratoses in vivo: a preliminary report.

BACKGROUND: Real-time near-infrared confocal laser scanning microscopy (CM) offers an unprecedented method for confirming the clinical diagnosis of actinic keratosis (AK) without biopsy. METHODS: Seven patients with clinically diagnosed AK underwent CM imaging over the lesion and over adjacent normal-appearing skin. Biopsy specimens were obtained from the presumed AKs in 4 patients. RESULTS: CM detected lesional pathologic features of hyperkeratosis (71%), lower epidermal nuclear enlargement and pleomorphism (100%), and architectural disarray (57%). In contrast, cytologic atypia and architectural disarray were apparent in one patient (17%) over the adjacent, clinically normal skin. Three of 4 biopsy specimens confirmed the clinical diagnosis of AK, whereas one revealed invasive squamous cell carcinoma. Without optimizing CM for imaging hyperkeratotic skin lesions, the limited depth of penetration reached the stratum basale in only 3 lesions, precluding detection of dermal invasion in the others. CONCLUSION: Depth of penetration currently imposes a major limitation on CM in the diagnosis of AKs, especially in hypertrophic and hyperkeratotic lesions, which are more likely to be malignant. However, CM may become an alternative to biopsy, and its limitations may be overcome by future technologic advances in optical penetration or by simply removing the hyperkeratotic stratum corneum.

Elucidating the pulsed-dye laser treatment of sebaceous hyperplasia in vivo with real-time confocal scanning laser microscopy.

BACKGROUND: Several case reports document successful treatment of sebaceous hyperplasia with the pulsed-dye laser. Moreover, noninvasive real-time confocal laser scanning microscopy elucidates the vascular nature of these lesions and their pathophysiologic response to treatment mediated by vessel coagulation. METHODS: Ten patients with 29 lesions of sebaceous hyperplasia were treated with 3 stacked 5-mm pulses of the 585-nm pulsed-dye laser at fluences of 7 or 7.5 J/cm(2). Confocal imaging was performed before and immediately after treatment, as well as at 2, 4, and 8 weeks of follow-up. RESULTS: The great majority of lesions responded to one treatment, with complete disappearance in 28%, decrease in diameter in 66%, and flattening in 93%. Although 28% recrudesced after initial involution, only 7% recurred completely. Three lesions became eroded or crusted, and 7 experienced cutaneous depressions before complete healing, but no scarring or pigmentary side effects were noted. Confocal imaging revealed a prominent "crown" of blood vessels surrounding the sebaceous duct and coagulation of these vessels with pulsed-dye laser treatment. However, the vessels reappeared during follow-up, and no noticeable morphologic changes in the sebaceous duct were noted. CONCLUSION: Vascular targeting of sebaceous hyperplasia can be monitored with real-time reflectance confocal microscopy. Most sebaceous hyperplasia regresses after one treatment with 3 stacked pulses of the 585-nm pulsed-dye laser. Whether this response is due to temporary ischemia induced by selective vessel destruction or nonspecific thermal diffusion beyond the vessels from pulse stacking has not been determined.

Complications of aesthetic laser surgery.

Aesthetic laser surgery is not risk free. It behooves the laser surgeon to become intimately familiar with the potential adverse effects of laser use to guard against and to minimize their occurrence. Moreover, patients must be thoroughly, clearly, and honestly educated about the procedure and its risks so that their expectations are realistic and so that any complications that do occur can be recognized early and treated appropriately. This review summarizes basic laser safety and discusses the nature of complications that may occur during continuous-wave, pulsed dye, pigment-specific, hair removal, and resurfacing laser procedures.

Reproducible measurements to quantify cutaneous involvement in scleroderma.

BACKGROUND AND DESIGN: Because the current assessment of scleroderma through clinical skin scoring is subjective and imprecise, we devised fully quantitative measures of cutaneous involvement. First, we developed image analysis software for calculating the density of dermal collagen from 58 scleroderma and 327 control biopsy specimens. Second, using a durometer gauge, we obtained measurements of skin hardness over 12 body regions for 13 patients with scleroderma and 100 controls. We obtained serial durometer measurements at 2-cm intervals over the arms of four patients with scleroderma, correlating them with blinded assessments of skin score. Third, we produced two-dimensional laser Doppler maps of cutaneous blood flow over the dorsal aspect of the hands of 10 patients with scleroderma and 16 controls and, with software, we determined the mean red blood cell flux, density of arteriolar islands, and percentage of avascular area at each measured site. RESULTS: Average collagen density was significantly higher in patients with scleroderma (88.5% +/- 6.9%) compared with that in controls (75% +/- 9.3%) (P < .001). Durometer measurements were significantly greater for patients with scleroderma (P < .05) over the finger, hand, wrist, forearm, and ventral aspect of the arm. In individual patients, the measurements paralleled with skin score. In patients with scleroderma, mean red blood cell flux (483.2 +/- 421.2 mV) and arteriolar island density (1.4 +/- 0.5/cm2) were significantly greater than were the control averages (276.3 +/- 146.3 mV [P < .03] and 1.0 +/- 0.5/cm2 [P < .013], respectively). CONCLUSIONS: Dermal collagen density and durometer measurements of skin hardness accurately quantify skin sclerosis in scleroderma and permit the determination of sclerotic borders, respectively. Increased cutaneous red blood cell flux and greater use of microvascular reserve reflect defects in vascular regulation inherent to the disease. These reproducible measurements will allow us to more precisely monitor the progression of scleroderma, evaluate its response to experimental treatments, and investigate its pathogenetic origins.