Laser treatment for Cafe-au-lait Macules: a systematic review and meta-analysis.

Nowadays, laser is the mainstay treatment for cafe-au-lait macules (CALMs), but no systematic review has been published to demonstrate the overall efficacy and it's still controversial which type of laser is optimal. Thus, we conduct the meta-analysis to evaluate the effectiveness and side effects of various types of lasers in treating CALMs. Original articles reporting the efficacy and side effects for CALMs in laser treatment were identified in PubMed, EMBASE, and Web of Science from 1983 to April 11, 2023. Using R software and the 'meta' package, meta-analysis was conducted for clearance and recurrence for evaluation of efficacy. And the occurrence of hypopigmentation and hyperpigmentation rate was pooled for safety evaluation. We used RoB2 and ROBINS-I tools to assess the risks of bias in RCT studies and non-RCT studies, respectively. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of the evidence. Nineteen studies involving 991 patients were included, which had a very low to moderate quality of evidence. The pooled 75% clearance rate was 43.3% (95% CI 31.8-54.7%, I2 = 96%), 50% clearance rate was 75% (95% CI 62.2-85.9%, I2 = 89%) and the recurrence rate was 13% (95% CI 3.2-26.5%, I2 = 88%). The pooled hypopigmentation and hyperpigmentation rates were 1.2% (95% CI 0.3-2.1%, I2 = 0%) and 1.2% (95% CI 0.3-2%, I2 = 0%), respectively. Subgroup analysis revealed that QS-1064-nm Nd:YAG laser treatment not only achieved more than 75% clearance rate in 50.9% of patients (95% CI 26.9-74.4%, I2 = 90%) but also resulted in the lowest hypopigmentation and hyperpigmentation rate of 0.5% (95% CI 0.0-2.5%, I2 = 26%) and 0.4% (95% CI 0.0-2.5%, I2 = 0%). To draw a conclusion, the laser treatment could reach an overall clearance rate of 50% for 75% of the patients with CALMs, for 43.3% of the patients, the clearance rate could reach 75%. When looking at different wavelength subgroups, QS-1064-nm Nd:YAG laser exhibited the best treatment capability. Laser of all the wavelength subgroups presented acceptable safety regarding of the low occurrence of side effects, namely, hypopigmentation and hyperpigmentation.

Comparison of the safety and efficacy of low fluence Q-switched 1064-nm and conventional Q-Switched 755-nm lasers in the treatment of café-au-lait macules: A prospective self-controlled trial.

BACKGROUND: Conventional high fluence Q-switched (HFQS) Alexandrite 755-nm are widely used in clinical café-au-lait macules (CALMs) treatment. There have been recent concerns regarding the efficacy and safety of low fluence Q-switched (LFQS) Nd: YAG 1064-nm lasers. OBJECTIVE: To evaluate the efficacy and safety of the conventional HFQS and LFQS laser in the treatment of CALMs. METHODS: Within 3 months, 20 patients underwent prospective self-controlled split-lesion treatments with HFQS once or twice depending on the recovery rate, and with LFQS six times biweekly. Then the more effective laser was selected for continued treatments. Efficacy outcomes were evaluated by a visual analog scale (VAS) biweekly during the comparative trail. Recovery process, side effects and recurrence were recorded during the trial and follow-up visit. Patient and physician preferences for laser selection were also recorded. RESULTS: The average VAS scores of areas treated with HFQS and LFQS were 2.92 ± 0.86 and 2.93 ± 1.13, respectively (p > 0.05). The most significant efficacy change of LFQS was after the fourth laser treatment (VAS score: 1.82-2.37, p < 0.001). 11 lesions treated with LFQS and 7 with HFQS achieved an optimal treatment response (3.67 ≤ VAS ≤ 4). Three patients relapsed on one side (one on LFQS, two on HFQS) and five on both sides. Adverse effects included temporary hypopigmentation, hyperpigmentation, uneven pigmentation, and mottled hypopigmentation. Doctors thought 80% of patients were suitable for LFQS. 70% of patients preferred LFQS posttreatment. CONCLUSIONS: The efficacy difference between the LFQS 1064-nm laser and HFQS 755-nm laser in treating CALMs in a 3-month comparative trial was statistically insignificant. LFQS is preferred by doctors and patients and is likely to help more patients achieve treatment efficacy than the HFQS within a short time, with fewer temporary adverse reactions, and a more even pigmentation. But it can cause mottled hypopigmentation. The LFQS had obvious lesion clearance after the fourth treatment.

Australian experience and practical approach to the 308-nm excimer light therapy in dermatology.

The monochromatic excimer light therapy (308-nm excimer laser and lamp) is used to treat focal dermatoses with inflammation or hypopigmentation. In Australia, despite excimer light therapy being a proven effective treatment for many cutaneous conditions, barriers such as access and affordability provide considerable limitations to patients. This study aims to retrospectively evaluate the different applications of excimer light therapy in treating dermatologic conditions within the Australian setting and provide practical information for its use.

Hypopigmented Mycosis Fungoides: A Clinical and Histopathology Analysis in 9 Children.

BACKGROUND: Hypopigmented mycosis fungoides (HMF) is an uncommon variant of mycosis fungoides. AIMS: To study the clinical and histopathology presentation in children with HMF. METHOD: We reviewed 9 children diagnosed with HMF. The clinical data were collected and analyzed. RESULT: Eight boys and 1 girl were included, with a median onset age of 7.4 year old and median age of diagnosis of 10.5 year old. Multiple hypopigmented patches were observed in all patients, and 5 patients exhibited multiple scaly erythema at the center of hypopigmented patches. Histopathology showed atypical lymphocytes with hyperchromatic, irregular, and cerebriform nuclei, infiltrated in the epidermis and dermis. Pautrier's microabscesses was noted in 6 of 9 patients, and papillary dermal fibroplasia was noted in 6 of 9 patients. CD8 predominance was detected in 4 of 6 patients. Four patients were simultaneously subjected to skin biopsy on hypopigmented patches and scaly erythema simultaneously. Compared with hypopigmented specimens, erythema biopsy detected deeper and denser infiltration of atypical lymphoid cells in 3 of 4 patients, higher CD4+/CD8+ ratio in 4 of 4 patients, more CD5 loss in 2 of 4 patients, and more CD7 loss in 2 of 4 patients. TCR gene monoclonal rearrangement was detected in 2 of 5 patients. Narrowband ultraviolet B phototherapy was applied in 7 patients. One of 7 patients achieved complete response, and 6 of 7 patients achieved partial response. No recurrence was noted with the median follow-up period of 6 months. CONCLUSION: HMF could occur in young patients, with indolent and benign course. HMF could gradually seem as scaly erythema based on hypopigmented patches. The histopathology indicated a more advanced stage of the scaly erythema lesions than hypopigmented patches.

Mechanisms of repigmentation induced by photobiomodulation therapy in vitiligo.

Photobiomodulation (PBM) therapy is based on the exposure of biological tissues to low-level laser light (coherent light) or light-emitting diodes (LEDs; noncoherent light), leading to the modulation of cellular functions, such as proliferation and migration, which result in tissue regeneration. PBM therapy has important clinical applications in regenerative medicine. Vitiligo is an acquired depigmentary disorder resulting from disappearance of functional melanocytes in the involved skin. Vitiligo repigmentation depends on available melanocytes derived from (a) melanocyte stem cells located in the bulge area of hair follicles and (b) the epidermis at the lesional borders, which contains a pool of functional melanocytes. Since follicular melanoblasts (MBs) are derived from the melanocyte stem cells residing at the bulge area of hair follicle, the process of vitiligo repigmentation presents a research model for studying the regenerative effect of PBM therapy. Previous reports have shown favourable response for treatment of vitiligo with a low-energy helium-neon (He-Ne) laser. This review focuses on the molecular events that took place during the repigmentation process of vitiligo triggered by He-Ne laser (632.8 nm, red light). Monochromatic radiation in the visible and infrared A (IRA) range sustains matrix metalloproteinase (MMP), improves mitochondrial function, and increases adenosine triphosphate (ATP) synthesis and O2 consumption, which lead to cellular regenerative pathways. Cytochrome c oxidase in the mitochondria was reported to be the photoacceptor upon which He-Ne laser exerts its effects. Mitochondrial retrograde signalling is responsible for the cellular events by red light. This review shows that He-Ne laser initiated mitochondrial retrograde signalling via a Ca2+ -dependent cascade. The impact on cytochrome c oxidase within the mitochondria, an event that results in activation of CREB (cyclic-AMP response element binding protein)-related cascade, is responsible for the He-Ne laser promoting functional development at different stages of MBs and boosting functional melanocytes. He-Ne laser irradiation induced (a) melanocyte stem cell differentiation; (b) immature outer root sheath MB migration; (c) differentiated outer root sheath MB melanogenesis and migration; and (d) perilesional melanocyte migration and proliferation. These photobiomodulation effects result in perifollocular and marginal repigmentation in vitiligo.

Hypopigmented Interface T-Cell Dyscrasia and Hypopigmented Mycosis Fungoides: A Comparative Study.

Hypopigmented interface T-cell dyscrasia (HITCD) is a distinct form of lymphoid dyscrasia that may progress to hypopigmented mycosis fungoides (HMF). We compared both diseases as regards their CD4/CD8 phenotype and expression of granzyme B and tumor necrosis factor-alpha (TNF-α) and how these are affected by narrow-band UVB (nb-UVB). The study included 11 patients with HITCD and 9 patients with HMF. They received nb-UVB thrice weekly until complete repigmentation or a maximum of 48 sessions. Pretreatment and posttreatment biopsies were stained using anti CD4, CD8, TNF-α, and granzyme B monoclonal antibodies. Epidermal lymphocytes were CD8 predominant in 54.5% and 66.7% of HITCD and HMF cases, respectively, whereas dermal lymphocytes were CD4 predominant in 63.6% and 66.7%, respectively. Significantly, more dermal infiltrate was encountered in HMF (P = 0.041). In both diseases, granzyme B was only expressed in the dermis, whereas TNF-α was expressed both in the epidermis and dermis. No difference existed as regards the number of sessions needed to achieve repigmentation or cumulative nb-UVB dose reached at end of study. (P > 0.05). Narrow-band UVB significantly reduced only the epidermal lymphocytes in both diseases (P ≤ 0.05) with their complete disappearance in 8 (72.7%) HITCD and 6 (66.7%) HMF cases. In both diseases, nb-UVB did not affect granzyme B or TNF-α expression (P > 0.05). In conclusion, both diseases share the same phenotype, with HITCD being a milder form of T-cell dysfunction. In both diseases, epidermal lymphocytes are mainly CD8-exhausted cells lacking cytotoxicity, whereas dermal cells are mostly reactive cells exerting antitumor cytotoxicity. Tumor necrosis factor-alpha mediates hypopigmentation in both diseases and prevents disease progression. Repigmentation after nb-UVB in both diseases occurs before and independently from disappearance of the dermal infiltrate.

Facial nevus depigmentosus getting remarkable repigmentation by treatment with a 308-nm excimer laser: A case report.

Nevus depigmentosus (ND) is a rare, congenital, nonprogressive depigmented lesion with irregular outline. To date, the few therapeutic approaches that have been developed to treat ND have yielded unsatisfactory results. We reported on a 6-month-old girl who presented with a ND on the right side of her face for 5 months. Treatment with a 308-nm excimer laser was started once a week at 300 mJ/cm2 and then was increased by 50-100 mJ/cm2 in each subsequent session until post-treatment erythema occurred. After 10 treatments, repigmentation in the lesion was evident and remained stable 1 month later at follow up. This case supports that the 308-nm excimer laser may be a good choice for the treatment of ND.

Excimer Light Treatment for Idiopathic Guttate Hypomelanosis: A Pilot Study.

BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a commonly acquired benign leukoderma characterized by multiple discrete, hypo- or depigmented macules often on extremities that can be aesthetically undesirable for patients. This is the first study using excimer laser for treatment. OBJECTIVE: To determine the effectiveness of excimer laser for repigmentation of idiopathic guttate hypomelanosis. METHODS AND MATERIALS: In this longitudinal, split-body controlled, single-blinded pilot study, 6 patients were treated with excimer laser for 12 weeks using the vitiligo protocol. Effectiveness was graded by the blinded observer scale through photographic comparisons at the end of the study. Participants also graded their progress at intervals during the study. A descriptive trend analysis and an ANOVA model were used to determine outcomes. RESULTS: Lesions that received the excimer treatment had significantly higher repigmentation by the end of the study compared with baseline and untreated lesions. CONCLUSION: Excimer laser treatments are already considered to be a safe modality for a variety of skin conditions. This study suggests that excimer is an effective treatment option with acceptable cosmetic outcomes for IGH.

Applications of the Excimer Laser: A Review.

BACKGROUND: The 308-nm excimer laser has been approved by the Food and Drug Administration for the treatment of psoriasis and vitiligo. Its ability to treat localized areas has led to many studies determining its potential in the treatment of focal diseases with inflammation or hypopigmentation. OBJECTIVE: To review the different applications of the 308-nm excimer laser for treating dermatologic conditions. METHODS AND MATERIALS: An extensive literature review was conducted by searching PubMed, MEDLINE, and ClinicalKey to find articles pertaining to dermatologic conditions treated with the 308-nm excimer laser. Articles published that contributed to new applications of the excimer laser were included, as well as initial studies utilizing the excimer laser. RESULTS: The outcomes and results were compiled for different dermatologic conditions treated with the excimer laser. CONCLUSION: The 308-nm excimer laser has a wide range of uses for focal inflammatory and hypopigmented conditions. Treatment is generally well tolerated, with few adverse reactions. Larger studies and studies evaluating the long-term effects of the 308-nm excimer laser are needed.

Additive effect of heat on the UVB-induced tyrosinase activation and melanogenesis via ERK/p38/MITF pathway in human epidermal melanocytes.

Heat is known as an environmental factor that causes significant skin pigmentation, but its effects on melanogenesis have been poorly studied. It has been shown that mitogen-activated protein kinase (MAPK) is involved in ultraviolet B (UVB) and stress-induced melanogenesis in melanocytes. In this study, we investigated the effects of heat and UVB, on melanocyte melanogenesis, differentiation, and MAPK phosphorylation. The results showed that heat (1 h at 40 °C for 5 days) increased cell dendrites, enlarged cell bodies, and induced extracellular signal-regulated kinases (ERK)/p38/MITF activation but did not influence melanogenesis of human epidermal melanocytes from skin phototype III. UVB irradiation (20 mJ/cm(2) for 5 days) induced melanogenesis and c-jun N-terminal kinases (JNK)/p38/MITF/tyrosinase activation in melanocytes from skin phototype III. UVB combined with heat resulted in much more significant tyrosinase activation and melanogenesis as compared with UVB alone in melanocytes from skin phototype III. Furthermore, heat treatment and UVB irradiation induced JNK, ERK, and p38 activation but not melanogenic and morphological changes in melanocytes from skin phototype I. These findings suggested that heat promoted melanocyte differentiation, probably via heat-induced ERK/p38/MITF/activation. Furthermore, heat had an additive effect on the UVB-induced tyrosinase activation and melanogenesis. These results provide a new clue for dermatologists for the treatment of hypopigmented skin disease with heat combined with UVB irradiation.