Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

Predicting Negative Outcomes of Cryolipolysis in Patients With and Without Raynaud Disease.

BACKGROUND: Cryolipolysis is an effective means of noninvasive fat reduction. There are numerous relative contraindications to cryolipolysis including scars, hernias, and cold-related disorders such as Raynaud disease, because cryolipolysis has a theoretical risk of exacerbating these conditions. OBJECTIVE: To examine predictors of negative outcomes of cryolipolysis, especially as it pertains to safety of cryolipolysis in patients with Raynaud disease. MATERIALS AND METHODS: A retrospective review of patients who received consultation for cryolipolysis was conducted and analyzed. RESULTS: Patients with Raynaud disease did not experience any exacerbations of their underlying condition after cryolipolysis. Side effects in all patients, regardless of medical history, were mild, temporary, and not associated with any predisposing factors. CONCLUSION: Cryolipolysis seems to be safe in patients with mild-moderate Raynaud disease.

Wounding Therapies for Prevention of Photocarcinogenesis.

The occurrence of non-melanoma skin cancer (NMSC) is closely linked with advanced age and ultraviolet-B (UVB) exposure. More specifically, the development of NMSC is linked to diminished insulin-like growth factor-1 (IGF-1) signaling from senescent dermal fibroblasts in geriatric skin. Consequently, keratinocyte IGF-1 receptor (IGF-1R) remains inactive, resulting in failure to induce appropriate protective responses including DNA repair and cell cycle checkpoint signaling. This allows UVB-induced DNA damage to proliferate unchecked, which increases the likelihood of malignant transformation. NMSC is estimated to occur in 3.3 million individuals annually. The rising incidence results in increased morbidity and significant healthcare costs, which necessitate identification of effective treatment modalities. In this review, we highlight the pathogenesis of NMSC and discuss the potential of novel preventative therapies. In particular, wounding therapies such as dermabrasion, microneedling, chemical peeling, and fractionated laser resurfacing have been shown to restore IGF-1/IGF-1R signaling in geriatric skin and suppress the propagation of UVB-damaged keratinocytes. This wounding response effectively rejuvenates geriatric skin and decreases the incidence of age-associated NMSC.

Physical modalities for treating acne and rosacea.

Physical modalities provide an important adjunct to medical treatment of acne and rosacea. In patients who cannot tolerate or fail medical treatments, physical modalities offer an alternative approach. For cases of acne scarring, phymatous changes of rosacea, and rosacea-associated telangiectasia, physical modalities such as laser and light treatments represent the treatment of choice. We will review the use of laser and light treatments, photodynamic therapy, and other physical modalities such as targeted therapies for the treatment of acne and rosacea.

Immediate skin responses to laser and light treatments: Warning endpoints: How to avoid side effects.

Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

Immediate skin responses to laser and light treatments: Therapeutic endpoints: How to obtain efficacy.

Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints.

Use of Photodynamic Therapy and Sterile Water to Target Adipose Tissue.

BACKGROUND: Neither photodynamic therapy (PDT) nor sterile water has not been well studied for the treatment of adipose tissue. OBJECTIVE: This investigation studied 2 different modalities, verteporfin PDT and sterile water, on adipose tissue compared with control. MATERIALS AND METHODS: Four light-skinned pigs were used. Test sites received verteporfin PDT or sterile water injection. Control sites received injection of verteporfin without PDT, normal saline injection, no intervention, exposure to laser only, or insertion of a needle or cannula only. Sites were evaluated clinically, by ultrasound, and with histology 4 to 6 weeks after treatment. RESULTS: There was a decrease in adipose tissue by ultrasound after verteporfin PDT (15%, p < .001) and sterile water (2%, p = .23). Verteporfin without PDT showed a decrease in adipose tissue (17%, p = .21). All other control sites showed an increase in adipose tissue. Histologically, verteporfin PDT and sterile water showed moderate damage (median Grade 2, p < .001) 4 to 6 weeks after intervention. CONCLUSION: Verteporfin decreased adipose tissue after treatment. Sterile water injection had a statistically significant effect on adipose tissue histologically but did not substantially decrease the adipose tissue by ultrasound 4 to 6 weeks after intervention. Longer follow-up may be needed.

Single blind, randomized, controlled trial of a lightening product with and without iontophoresis versus tretinoin and vehicle for hyperpigmentation.

BACKGROUND: Hyperpigmentation is a common concern and has many causes including lentigines and melasma. Currently available topical products for hyperpigmentation are limited by their potential for irritation, lack of demonstrated efficacy or regulatory concerns. OBJECTIVE: To compare the efficacy of a new skin lightening product with and without iontophoresis to a known effective product (tretinoin) and placebo on hyperpigmentation caused by lentigines and/or melasma. Secondary objectives included an assessment of the product's effects on the appearance of rhytides and roughness. METHODS AND MATERIALS: Eighty subjects were randomized into one of four treatment groups: proprietary lightening product, proprietary lightening product with iontophoresis, tretinoin 0.05% cream, or vehicle control. Seventy-four subjects completed all study visits. Blinded assessments of subjects were performed at each visit under ambient and Wood's light. RESULTS: The proprietary skin lightening product improved facial hyperpigmentation versus placebo under ambient light (P= 0.05) and Wood's lamp (P= 0.01) examination. Tretinoin also improved facial hyperpigmentation versus placebo under Wood's lamp (P= 0.01). The proprietary product was better tolerated than tretinoin, with fewer subject reported side effects. CONCLUSION: The investigational product was effective and may be better tolerated than tretinoin cream.

A review of lasers and light for the treatment of onychomycosis.

BACKGROUND AND OBJECTIVE: Onychomycosis is a common fungal infection that affects many individuals. Systemic therapies are effective, but are limited by their side effects and potential for hepatotoxicity. Topical therapies have less serious side effects, yet provide only limited efficacy due to their inability to penetrate the nail plate. These limitations have led to the investigation of laser and light-based modalities as alternative treatment options for onychomycosis. This article will provide an overview and critical assessment of the field of laser and other energy-based treatments for onychomycosis. STUDY DESIGN/MATERIALS AND METHODS: A literature search was conducted on laser and light-based treatments for onychomycosis. RESULTS: Early data are promising, however, many of these studies are small or poorly designed. CONCLUSION: Further evaluation and larger studies are needed to determine the optimal light source, pulse duration, and treatment schedule for long-term success.

Aquagenic wrinkling of the palms: A case report and literature review.

Aquagenic wrinkling of the palms (AWP) is a condition that results in pain and edema of the hands after exposure to water. We describe a 32-year-old woman who presented with a several-year history of AWP. She was unable to tolerate a 20 percent aluminum chloride solution because of irritation, but a gel formulation of 15 percent aluminum chloride controlled her symptoms without side effects.

Effects of non-invasive, 1,210 nm laser exposure on adipose tissue: results of a human pilot study.

BACKGROUND AND OBJECTIVES: Laser radiation (1,210 nm) has been previously shown to be capable of selective photothermolysis of adipose tissue in vitro when applied non-invasively. The objective of this pilot study was to evaluate the in vivo effects of this laser in human subjects. STUDY DESIGN/MATERIALS AND METHODS: Twenty-four adult subjects were exposed non-invasively on the abdomen to a 1,210 nm laser at fluences of 70, 80, and 90 J/cm(2), with a 10 mm spot size, 5 seconds pre-cooling, and 3 seconds exposure duration delivered with parallel contact cooling. There was an impairment of the skin-cooling device during the study. Exposure and control sites were biopsied at either 1-3 days or 4-7 weeks. Tissue was processed for nitroblue tetrazolium chloride (NBTC) staining, a marker for thermal damage, and hematoxylin and eosin (H&E) staining. RESULTS: Laser exposures were painful, requiring local anesthesia in most subjects, but otherwise well tolerated. At 1-3 days after exposure, there was a fluence-dependent loss of NBTC staining in the fat and dermis. In 2 of 14 subjects (2 of 42 exposure sites) evaluated at 1-3 days after exposure, epidermal damage was noted within a small portion of the test site, likely due to impaired contact cooling. At 4-7 weeks, lipomembranous changes of the fat were seen in 89% of test sites and 33% of control sites. CONCLUSIONS: This in vivo study shows histologic evidence of laser-induced damage of fat. With further development, this might become a useful treatment for disorders involving the fat and/or lower dermis.

An evidence-based assessment of treatments for cellulite.

Cellulite, a skin surface change that is nearly ubiquitous in women, is a condition that remains elusive to treatment. In fact, no treatment is completely successful as none are more than mildly and temporarily effective. Despite the lack of evidence to support efficacy, treatment options continue to proliferate. This article will briefly review the currently available data about cellulite treatments including noninvasive devices such as massage, radiofrequency, and laser and light-based treatments; invasive modalities including liposuction, mesotherapy, and subcision; and other treatments including topical creams and carboxy therapy.

Persistent erythema multiforme and CMV infection.

Persistent erythema multiforme is a rare disorder with only 23 known cases reported in the literature. Persistent erythema multiforme has been reported in association with Epstein-Barr virus, herpes virus, hepatitis C virus, influenza, inflammatory bowel disease, and a variety of neoplasms. To our knowledge, this case is the first case of persistent erythema multiforme reported in association with cytomegalovirus infection.

Fractional photothermolysis: treatment of facial and nonfacial cutaneous photodamage with a 1,550-nm erbium-doped fiber laser.

PURPOSE: To evaluate the safety and effectiveness of a novel nonablative 1,550 nm erbium-doped fiber laser in the treatment of facial and non-facial photodamaged skin. METHODS: 50 patients with mild to moderate cutaneous photodamage, rhytides, and dyspigmentation received 3 successive treatments at 3-4 week intervals with a 1,550 nm erbium-doped fiber laser (Fraxel, Reliant Technologies Inc., San Diego, CA). Clinical improvement of treatment areas was independently determined by two masked assessors' evaluations of comparative photographs at baseline and 3, 6, and 9 months post-treatment using a quartile grading scale. Patient satisfaction surveys were also obtained at each follow-up visit. RESULTS: Mean clinical improvement at 3 months for the face was 2.23 and 1.85 for non-facial skin (p<0.001). Mean improvement at 6 months was 2.10 for the face and 1.81 for non-facial skin (p<0.001). Mean improvement at 9 months was 1.96 for the face and 1.70 for non-facial skin (p<0.001). At least 51% to 75% improvement in photodamage at the 9-month follow-up was achieved in 73 and 55% of facial and non-facial treated skin, respectively. Side effects were limited to transient erythema and edema in the majority of patients. No prolonged pigmentary changes or scarring were observed. Patient satisfaction surveys mirrored the observed clinical effects. CONCLUSION: The nonablative 1,550 nm erbium-doped fiber laser is an effective treatment for facial and non-facial photodamage, rhytides, and dyspigmentation with a favorable recovery and side effect profile.

Laser hair removal.

Since 1996, there have been numerous advances in hair laser removal that utilize melanin as a chromophore. All of the devices on the market may be used in patients with light skin (phototypes I-III) and yield hair reduction near 75%. The ruby (694 nm) laser, alexandrite (755 nm) laser, and diode (810 nm) laser, as well as intense pulsed light are commonly used devices for hair laser removal. The long-pulsed Nd:YAG (1064 nm) laser represents the safest device for hair removal in dark-skinned patients because of its long wavelength, although the diode laser, alexandrite laser, and intense pulse light may be used. For treatment of light hair, combination radiofrequency and optical devices as well as photodynamic therapy are under investigation.