Mode of action of glycolic acid on human stratum corneum: ultrastructural and functional evaluation of the epidermal barrier

Alpha-hydroxy acids (AHA) such as glycolic acid have recently been used extensively in cosmetic and dermatological formulas. In low concentration (2– 5%) glycolic acid is believed to facilitate progressive weakening of cohesion of the intercellular material of the stratum corneum (SC), resulting in uniform exfoliation of its outermost layers (the stratum disjunctum). Since thinning of the SC as well as changes of intercellular lipids could theoretically compromise the barrier functions of the skin, we investigated the mode of AHA action on the SC to determine whether enhanced desquamation compromises the barrier structures of the SC and changes transepidermal water loss (TEWL) values. Electron microscopy of the epidermis biopsied from the volar forearm of human volunteers after 3 weeks of treatment with a 4% glycolic acid formulation twice daily was employed to evaluate 1) epidermal morphology and thickness of the SC, (2) the lamellar body and SC lipid bilayer organization, and (3) desquamative events based on degradation of desmosomes. TEWL values and SC hydration were recorded prior to and at the end of the study. Electron microscopy revealed no ultrastructural changes in the nucleated layers of the epidermis. The lamellar body (LB) secretory system in the stratum granulosum (SG), and intercellular lipid lamellae in the SC in both vehicle- and glycolic acid-treated samples were comparable to normal human SC. Within the SC, enhanced desmosomal breakdown, promoting loss of cohesion and desquamation, was restricted to the stratum disjunctum while desmosomes of the stratum compactum were unaffected. Treated areas displayed histologically, a more compact appearing SC. TEWL values remained unchanged in glycolic acid- and vehicle-treated skin. Our findings indicate that the barrier structures of the SC are not disrupted by glycolic acid formulations at the concentration used. One of the mechanism of action of AHA on the SC seemed to be a „targeted“ desmosomal (corneosomal) action without compromising the barrier structures of the skin. Received: 20 November 1996     

Two 14-epi analogues of 1,25-dihydroxyvitamin D<Subscript>3</Subscript> protect human keratinocytes against the effects of UVB

In search of photoprotective agents, we recently demonstrated a protective effect of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] against different events mediated by ultraviolet B (UVB) in human keratinocytes. Pharmacological doses of 1,25(OH)₂D₃ were required to obtain significant UVB protection; however, these doses cannot be used in vivo due to the calcemic properties of 1,25(OH)₂D₃. Therefore, we evaluated the photoprotective capacities of two low-calcemic 14-epi analogues of 1,25(OH)₂D₃, 19-nor-14-epi-23-yne-1,25(OH)₂D₃ (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)₂D₃ (TX 527). Using cultured human keratinocytes, we investigated the influence of TX 522 and TX 527 on two hallmark events in UVB-irradiated keratinocytes: the induction of apoptosis and the production of interleukin-6 (IL-6). Treatment of the keratinocytes with TX 522 or TX 527, 24 h before irradiation, resulted in a significant and dose-dependent reduction of both UVB-induced apoptosis and IL-6 production. Both analogues were equally efficient in their anti-UVB effects and at least 100 times more potent than 1,25(OH)₂D₃. We further demonstrated that metallothionein (MT) mRNA expression was clearly induced by 1,25(OH)₂D₃ and both analogues. MT acts as a radical scavenger in oxygen-mediated UVB injury and its induction may therefore be relevant for the anti-UVB effects of 1,25(OH)₂D₃ and both analogues. Taken together, these findings create new perspectives for the use of active vitamin D analogues as photoprotective agents.     

Effectiveness of CO2 laser with subcision in patients with acne scars

Background: Post-acne facial scarring has always been a challenge to treat. It requires multiple therapeutic modalities as single modality is not hundred percent effective. Therefore, we have combined CO₂ laser resurfacing with subcision in patients with acne scars for better results. Objectives: The aim is to study the effectiveness and side effects of CO₂ laser with subcision in patients with atrophic acne scars. Methods: Fifty patients were selected for the study. Baseline grading was done with Goodman and Baron grading system. Twenty-five patients were randomly selected for subcision followed by CO₂ laser and the remaining patients were selected for CO₂ laser alone. The treatment was done for four sessions at 4-week interval. Clinical photographs were obtained for evaluation. Results: CO₂ laser with subcision showed excellent response in grade-2 and -3 acne scars. Statistically there is a significant difference between CO₂ laser following subcision and CO₂ laser alone at 5% level (p < 0.05). Both procedures were well tolerated with minimal side effects. Conclusion: The highly versatile CO₂ laser is useful for treating acne scars. Subcision prior to the CO₂ laser procedure showed better improvement when compared to CO₂ laser alone. Thus, in acne scars, multiple therapeutic modalities achieve better results.     

Treatment of striae distensae with needling therapy versus CO2 fractional laser

Background and objectives: Striae are atrophic dermal scars with overlying epidermal atrophy causing cosmetic concern. This study assesses and compares the efficacy and safety of needling therapy versus CO2 fractional laser in treatment of striae. Methods: Twenty Egyptian female patients with striae in the abdomen and lower limbs were involved in the study. The patients were treated with needling therapy and CO₂ laser every 1 month for 3 sessions. Follow-up by digital photography and skin biopsy was conducted at baseline and 6 months after treatment. Clinical improvement was assessed by comparing photographs and patient's satisfaction before and after treatment. Results: Nine of 10 (90%) needle-treated patients showed improvement. Among them, 3 (30%) had good, 4 (40%) had fair, and 2 (20%) had poor improvements; however, 1 (10%) did not show any improvement after the treatment. In CO₂-laser treated patients, 5 of 10 (50%) of the patients showed clinical improvement; 1 (10%) were good, 3 (30%) were fair, and 1 (10%) were poor; however, 5 (50%) did not show improvement. Conclusion: The results support the use of microneedle therapy over CO₂ lasers for striae treatment.     

Clinical trial of a pinpoint irradiation technique with the CO2 laser for the treatment of atrophic acne scars

Ablative laser resurfacing is an effective treatment for atrophic acne scars. However, it often induces complications such as edema, prolonged erythema, scarring and hyperpigmentation. Therefore, a new concept of laser treatment called fractional photothermolysis has been designed to create microscopic thermal wounds to achieve skin rejuvenation treatment of atrophic acne scars. This study was designed to prospectively evaluate the use of a technique similar to fractional photothermolysis using only the standard CO₂ laser without the fractional laser device in the treatment of atrophic scars and demonstrates it as a safe, effective and economical treatment option. Clinical improvement was achieved in all 35 patients with minimal adverse effects.     

Comparing the effectiveness of fractional CO2 laser and the combination therapy with micro-needling and topical 10% trichloroacetic acid to remove infra-orbital dark circles in Tehran women

Background: Infra orbital dark circles are now recognized as being a cosmetic problem that should be considered in treatment issue. The present study aimed to assess and compare the clinical efficiency of the combination of micro-needling and 10% trichloroacetic acid (TCA) cream as well as carbon dioxide laser in the management of infra-orbital dark circles. Methods: This randomized clinical trial was performed on women aged 28–62 years who complained of infra-orbital dark circles. The patients were randomly assigned to be treated with micro-needling combined with 10% TCA cream topically or CO₂ laser. The treatment period in each group included three sessions with an interval of one month between sessions. The assessment was based on both subjective and objective methods. Results: the mean of ΔE (the difference in the intensity of darkening at infra-orbital points and other points of the face) was significantly higher in the laser group than in the other group in all sessions. The patients who were treated with laser were found to have a higher level of satisfaction in the fifth visit when compared to those who received the other treatment method. Conclusion: Regarding clinical effectiveness and the patients’ compliance, fractional CO₂ laser was more preferred in the combination therapy with micro-needling and topical TCA for removing infra-orbital dark circles.     

Treatment of acne scarring with fractional CO2 laser

Abstract

Background: Fractional ablative CO₂ laser therapy is based on the theory of fractional photothermolysis. It can be effective in treating acne scars in a less invasive fashion than conventional ablative CO₂ laser therapy. Objective: In this clinical study, the safety and efficacy of a novel CO₂ fractional ablative laser was investigated for the treatment of facial atrophic acne scarring in Chinese individuals. Materials and methods: A total of 31 patients (11 females, 20 males, Fitzpatrick skin phototypes III–IV) with facial acne scarring received three sequential fractional treatments over a 6-month period. Outcome measurements included blinded evaluations of before and after photographs by two physicians at 3 and 12 months after the final treatment. Global improvement was noted as well as any untoward events. Results: At the 12 months follow-up time period, 12.9% of the patients showed excellent improvement in their acne scars, while 38.71% noted good to fair results. The clinical response at the 12-month follow-up visit tended to be better than at the 3-month follow-up visit, but was not statistically significant. Four patients experienced post-treatment and transient PIH but three patients were noted to have prolonged erythema. There was no evidence hypopigmentation or worsening of the scarring in any of the study patients. Conclusion: This high-energy pulsed and cool-scanned fractional ablative CO₂ laser system is safe and effective for facial atrophic acne scarring. Improvement in scarring was noted in the majority of patients with minimal discomfort and minimal downtime. Continued improvement over time is also an important clinical finding.     

Combined use of fractional CO2 laser and radiofrequency waves to treat acne scars: A pilot study on 15 patients

Abstract

Fractional laser resurfacing has become an important technique in the management of a number of skin conditions, such as photoaging and scars. A variety of laser wavelengths and delivery systems have been introduced to improve immediate and long-term therapeutic results. The simultaneous emission of CO₂ laser and radiofrequency waves combines epidermal coagulation for a resurfacing effect and dermal denaturization for deeper remodelling. The authors present this new machine together with a preclinical histological study and pilot study on 15 patients suffering from acne scars.     

The efficacy and safety of subcision using CO2 gas combined with fractional laser for acne scars: Clinical and microscopic evaluation

Background: Various modalities have been used to treat acne scars. CO₂ fractional laser is an effective and commonly used treatment. CO₂ gas injection into the dermis by needle with high pressure can cause fibrotic collagen breakage, producing the effects of subcision. CO₂ also stimulates collagen synthesis by increasing neovascularization and releasing oxygen. Objective: This study evaluated the efficacy and the safety of the combined treatment with CO₂ gas subcision and CO₂ fractional laser for acne scars. Methods and materials: Fourteen patients with acne scars were treated with three sessions of CO₂ gas subcision at 2-week intervals and two sessions of fractional laser at 4-week interval. The clinical improvement was assessed using a 4-point scale. For histologic analysis, punch biopsy was performed before and after treatment in 10 patients. Results: All patients experienced clinical improvements. Excellent, marked, moderate, and mild response was achieved in 1 (7%), 8 (57%), 4 (29%), and 1 patient (7%), respectively. Histologic evaluation of the biopsy specimens showed increased dermal collagen with dermal thickening and elastic fiber straightening in the reticular dermis after the treatment. Conclusion: The combination therapy with CO₂ gas subcision and fractional laser was satisfactory and safe for treating acne scars.

Abbreviation and acronym:

CO₂: Carbon dioxide

GAS: Global assessment scale

H&E: hematoxylin and eosin; SD: standard deviation     

The efficacy of fractional carbon dioxide (CO2) laser combined with terbinafine hydrochloride 1% cream for the treatment of onychomycosis

Background: Although systemic and topical antifungal agents are widely used to treat onychomycosis, oral medications can cause adverse effects and the efficacy of topical agents is not satisfying. Currently, laser treatment has been studied for its efficacy in the treatment of onychomycosis. Our study was aimed to evaluate the efficacy of fractional carbon dioxide (CO₂) laser treatment combined with terbinafine cream for 6 months in the treatment of onychomycosis and to analyze the influencing factors. Methods: A total of 30 participants (124 nails) with clinical and mycological diagnosis of onychomycosis received fractional CO₂ laser treatment at 2-week interval combined with terbinafine cream once daily for 6 months. The clinical efficacy rate (CER) was assessed from the percentage of fully normal-appearing nails or nails with ≤5% abnormal appearance, and the mycological clearance rate (MCR) was assessed from the percentage of nails with negative fungal microscopy. Results: The CER was evaluated at 3 time points: at the end of treatment (58.9%), at 1 month after the last treatment (63.5%), and at 3 months after the last treatment (68.5%). The MCRs at 1 month and 3 months after the last treatment were 77.4 and 74.2%, respectively. The evaluation of influencing factors showed significantly higher CER (p < 0.05) in nails of participants with age <50 years, distal lateral subungual onychomycosis (DLSO), superficial white onychomycosis (SWO), nail thickness <2 mm, affected first-to-fourth finger/toenails, Trichophyton rubrum, and Trichophyton mentagrophytes. All participants experienced tolerable mild burning sensation during laser treatment, but there were no other adverse reactions reported. Conclusions: Fractional CO₂ laser treatment combined with terbinafine cream for 6 months was an effective and safe method for the treatment of onychomycosis. There were 5 factors that positively influenced the treatment outcome: age, clinical type of onychomycosis, nail thickness, involved nail, and species of fungus.     

Vagarious successful treatment of recalcitrant warts in combination with CO2 laser and imiquimod 5% cream

Abstract

Background. Imiquimod 5% cream is widely regarded as a safe and effective option when treating recalcitrant warts, owing to the ointment's negligible side effects. However, our observations highlighted case of a patient incurring severe adverse reactions due to application of the cream, although the treatment proved successful in curing recalcitrant warts which had developed on the external auditory canal and external ear. Methods. All lesions were entirely removed with short-pulsed CO₂ laser. As soon as the wound-healing process was completed, imiquimod 5% cream was self-applied on the healing wounds once daily for 5 days per week in a total of 2 weeks. Results. The patient appeared normal after the CO₂ laser treatment and experienced severe redness, itching, exudation, and incrustation after a 2-week imiquimod 5% cream therapy. All lesions showed no recurrence during the 12-month followed-up process. Conclusions. We concluded that a feasible treatment modality to cure recalcitrant cutaneous warts is in combination of CO₂ laser and imiquimod. Immunoenhancement plays an important role in the treatment of recalcitrant warts.     

A systematic review of comparative studies of CO2 and erbium:YAG lasers in resurfacing facial rhytides (wrinkles)

Background: Laser resurfacing is used to minimize wrinkles, solar scars and sequelae of acne. Objective: Purpose of the systematic review was to compare resurfacing outcomes of CO₂ laser and erbium: yttrium aluminium garnet (erb:YAG) laser therapies. Materials and methods: Medline, Cochrane Library, EMBASE and Google Scholar databases were searched until 9 April 2015 using the following terms: laser, carbon dioxide/CO₂, facial wrinkles, rhytides and erbium-doped yttrium aluminium garnet/erbium:YAG/Er:YAG. Two-armed controlled split faced studies that compared CO₂ laser and erbium:YAG laser in patients with mild-to-moderate facial wrinkles or rhytides were included. Results: The pooled data in this study and findings of other studies support the greater efficacy with the CO₂ laser in improving facial wrinkles, but the erb:YAG laser was associated with a better complication profile compared with the CO₂ laser. Except one case of hypopigmentation, other complications (i.e., erythema, hyperpigmentation and crusting) and their rates were reported by studies examining both lasers. Conclusion: In general, the CO₂ laser appeared to be more efficacious then the erb:YAG laser in treating facial wrinkles. Both lasers treatments were well tolerated.     

Comparison of Q-switched Nd:YAG laser alone versus its combination with ultrapulse CO2 laser for the treatment of black tattoo

Background: Q-switched lasers are conventionally used for the treatment of black tattoo. However, they require multiple sittings, and the response may be slow due to competing epidermal pigment in dark skin. Objective: To compare the efficacy of Q-switched Nd:YAG laser alone with its combination with ultrapulse CO₂ for the removal of black tattoo. Materials and methods: Sixty patients with black tattoo were randomized into two groups viz., group A and group B. Group A was treated with QS Nd:YAG laser (1064 nm) alone, and group B received combination of ablative ultrapulse CO₂ followed by fixed-dose QS Nd:YAG laser (1064 nm), at 6-week interval for a maximum of 6 sittings. After each sitting, 3 independent physicians noted percentage of improvement that was evaluated using visual analogue scale (VAS) and grading system for tattoo ink lightening (TIL). Results: Combination laser (group B) showed statistically significant improvement in mean VAS score in the last 2 noted visits as compared to 1st session (p < 0.007, p < 0.001) and TIL mean score in last three noted visits as compared to 1st session (p < 0.008, p < 0.020, and p < 0.004). There was no statistically significant difference in the side effect profile of both the groups. Conclusion: For refractory professional tattoos, combination of ultrapulse CO₂ laser and QS Nd:YAG laser is superior to QS Nd:YAG laser alone.     

Treatment of hypertrophic scars and keloids with a fractional CO2 laser: A personal experience

Abstract

Keloids and hypertrophic scars are both abnormal wound responses in predisposed individuals but they differ in that keloids extend beyond the original wound and almost never regress, while hypertrophic scars remain within the original wound and tend to regress. How keloids grow is not totally clear because there is no animal model; in fact, keloids affect only humans. Different injuries can result in keloids, including burns, surgery, ear piercing, lacerations, abrasions, tattooing, vaccinations, injections, insect bites and any process causing skin inflammation (chicken pox, acne, folliculitis, zoster). Skin or wound tension is considered a critical factor in the formation of keloids and hypertrophic scars. This study is based on eight consecutive patients (four females and four males, F:M = 1:1) with a total of 12 keloids. All of whom were treated monthly with a MiXto SX CO₂ laser, using 13 W of power, 8 SX of index and 40% coverage (density) in combination with Same Plast Gel^® twice a day. Each scar required 12 treatments, and all the patients, followed up for 1 year after the last treatment, had optimum results and no recurrence.     

Successful treatment of malar dermal melasma with a fractional ablative CO2 laser in a patient with type V skin

Abstract

Background/Objective: Melasma is a common disorder of hypermelanosis, and although numerous treatment modalities have been employed, many cases are refractory to treatment or the improvement after therapy is temporary. Methods: The clinical files, treatment parameters, and photographs of a 59-year-old female with black skin with refractory malar dermal melasma treated using a fractionally ablative CO₂ laser (Affirm 10 600 nm) for seven sessions were carefully reviewed. Results: After treatment, clinical improvement was achieved. Conclusion: The fractional ablative CO₂ laser is a potentially safe and effective modality for the treatment of dermal melasma in Fitzpatrick type V skin.     

Fractional carbon dioxide (CO2) laser combined with topical tretinoin for the treatment of different forms of cystic acne

Nodulocystic acne is prone to scarring and difficult to treat with treatments other than oral isotretinoin. The aim of this article is to discuss the role of a single session of a fractional carbon dioxide (CO₂) laser combined with a topical treatment with a tretinoin and antibiotic gel for a month as a successful treatment to improve nodulocystic acne and chronic microcystic acne. Two cases were involved: the first with nodulocystic acne lesions that persisted after oral retinoids and the second with chronic microcystic acne resistant to topical treatments. After only one session of treatment with the CO₂ laser and the topical treatment, a complete healing of the nodulocystic acne lesions was observed with minimal secondary effects. The microcystic acne showed great improvement. No other topical or oral treatment was needed. This treatment could be a safe and effective treatment for nodulocystic acne lesions and microcystic acne when other treatments fail. More studies should be performed to confirm our results.     

Verruca plana as a complication of CO2 laser treatment: A case report

Carbon dioxide (CO₂) laser treatment is a common therapeutic modality for many dermatologic conditions. It uses a high energy, infrared beam of light, which selectively targets water-containing tissue resulting in controlled ablative resurfacing. This modality, however, can manifest significant cosmetic side effects. Here we report a case of verruca plana manifesting as a response to CO₂ laser treatment. A 74-year-old female with recent Mohs surgery for a basal cell carcinoma, presented for full-face-fractionated CO₂ treatment to address her surgical scars in addition to treating her mild diffuse actinic damage. Six weeks post treatment, the patient developed erythematous thin plaques over the areas that had been treated. Histology was consistent with verruca plana. Lesions showed mild improvement with topical tretinoin. Verruca plana are benign and typically self-limited; however, they can present a significant cosmetic burden to patients and are an important complication to consider when performing elective cosmetic procedures.     

Congenital melanocytic nevus on the lower eyelid treated with continuous wave and superpulsed CO2 laser followed by erbium laser

There are several therapeutic options to treat congenital melanocytic nevi. The motivations for the treatment of small- to medium-sized congenital nevi located on the face or other sensitive areas are frequently cosmetic. The choice of therapy depends on the operator’s expertise and on the likelihood of improved cosmesis. We report a case of a medium-sized congenital nevi located on the lower eyelid, successfully treated with a combination of ablative lasers with a single surgical procedure. We achieved an excellent clinical and cosmetic result. No scarring, distortion, or recurrence were observed.