Epidermal Lesions Research Articles

Treatment of flat and elevated pigmented disorders with a 755-nm alexandrite picosecond laser: clinical and histological evaluation.

The novel picosecond lasers, initially developed for faster tattoo removal, have also shown great efficacy in endogenous pigmentary disorders. To describe the efficacy and safety profile of an alexandrite (755-nm) picosecond laser in a wide range of pigmented flat and elevated cutaneous lesions. A retrospective study was performed in which we collected all the clinical images of patients treated with the 755-nm alexandrite picosecond laser for 12months (November 2016-November 2017). Clinical features were obtained from their medical charts. Patients treated for tattoo removal were excluded. All the images were analyzed by three blind physicians attending to a visual analogue scale (VAS) from 0 to 5 (0, no change; 1, 1-24% clearance; 2, 25-49% clearance; 3, 50-74% clearance; 4, 75-99% clearance; 5, complete clearance). Patient satisfaction was obtained from a subjective survey including four items: very satisfied, satisfied, non-satisfied, and totally dissatisfied. Thirty-seven patients were included (12 males; 25 females). The mean age of the study was 42.35years. Twenty-five patients (68%) were treated for different pigmented flat disorders such as solar and mucosal lentigines (5), stasis dermatitis (4), or nevus of Ota (4), among other diagnoses. Twelve patients (32%) were treated for epidermal elevated lesions such as warts (5), epidermal nevi (2), and seborrheic keratosis (3), among other elevated lesions. Mean number of laser treatment was 3.02 sessions while mean follow-up after last laser treatment was 4.02months. Mean VAS score of the three observers was 3.44 (61% of clearance) for pigmentary flat disorders and 3.60 (67%) for elevated lesions. Adverse effects reported were mild blistering in the first 2-5days following laser treatment in some of the patients. Overall satisfaction among the patients included was high. The novel 755-nm picosecond alexandrite laser is effective not only for the resolution of pigmented flat lesions of different nature but also for the treatment of the more difficult elevated pigmented lesions.

Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans

Amyloidosis cutis dyschromica (ACD) is a distinct form of primary cutaneous amyloidosis characterized by generalized hyperpigmentation mottled with small hypopigmented macules on the trunks and limbs. Affected families and sporadic case subjects have been reported predominantly in East and Southeast Asian ethnicities; however, the genetic cause has not been elucidated. We report here that the compound heterozygosity or homozygosity of GPNMB truncating alleles is the cause of autosomal-recessive ACD. Six nonsense or frameshift mutations were identified in nine individuals diagnosed with ACD. Immunofluorescence analysis of skin biopsies showed that GPNMB is expressed in all epidermal cells, with the highest staining observed in melanocytes. GPNMB staining is significantly reduced in the lesional skin of affected individuals. Hyperpigmented lesions exhibited significantly increased amounts of DNA/keratin-positive amyloid deposits in the papillary dermis and infiltrating macrophages compared with hypo- or depigmented macules. Depigmentation of the lesions was attributable to loss of melanocytes. Intracytoplasmic fibrillary aggregates were observed in keratinocytes scattered in the lesional epidermis. Thus, our analysis indicates that loss of GPNMB, which has been implicated in melanosome formation, autophagy, phagocytosis, tissue repair, and negative regulation of inflammation, underlies autosomal-recessive ACD and provides insights into the etiology of amyloidosis and pigment dyschromia.

Re-appraisal of keratinocytes' role in vitiligo pathogenesis

Background:Vitiligo is a common pigmentary disorder. Studies on its pathogenesis extensively investigated melanocytes' abnormalities and few studies searched for keratinocytes' role in disease development. Liver X receptor-α (LXR-α) is a member of nuclear hormone receptors that acts as a transcription factor. Its target genes are the main regulators of melanocyte functions.Aim:The aim of this study is to investigate keratinocytes' role in vitiligo pathogenesis through immunohistochemical expression of LXR-α in lesional, perilesional, and distant nonlesional vitiligo skin.Materials and Methods:This case–control study was carried out on 44 participants. These included 24 patients with vitiligo and 20 age- and sex-matched normal individuals as a control group. Biopsies, from cases, were taken from lesional, perilesional, and distant nonlesional areas. Evaluation was done using immunohistochemical technique.Results:Keratinocyte LXR-α expression was upregulated in the lesional and perilesional skin (follicular and interfollicular epidermis) compared with control skin (P <0.001 for all). There was significant association between higher histoscore (H-score) in lesional epidermis (P <0.001) and in hair follicle (P =0.001) and the presence of angiogenesis. There was significant association between higher H-score in lesional epidermis and suprabasal vacuolization (P =0.02). No significant association was found between H-score or expression percentage and clinical data of selected cases.Conclusion:LXR-α upregulation is associated with keratinocyte damage in vitiligo lesional skin that leads to decreased keratinocyte-derived mediators and growth factors supporting the growth and/or melanization of surrounding melanocytes. Therefore, melanocyte function and survival are affected.

Reduced immunohistochemical expression of CCN3 in vitiligo.

Defective adhesion seems to be involved in the chronic loss of melanocytes observed in vitiligo. Recent findings showed an association of genetic variants of an adhesion gene with vitiligo and reduced immunohistochemical expression of some adhesion molecules in vitiligo skin. To compare CCN3 immunohistochemical expression in lesional and non-lesional epidermis of individuals with vitiligo. A total of 66 skin specimens from 33 volunteers with vitiligo were analyzed by immunohistochemistry using anti-CCN3 antibodies. Absence of topical or systemic treatment for vitiligo over the previous 30 days and availability of an area of non-lesional skin for biopsy at least 15 cm away from any vitiliginous macules were the main inclusion criteria. A significant reduction of CCN3 expression was observed in lesional skin as compared to non-lesional skin (P = 0.001). Paraffin embedded skin samples do not allow investigation by molecular biology methods. Not all samples allowed analysis due to the lamina preparation technique. Complete clinical data was not available for all patients. Our results support the hypothesis of impaired cell adhesion in vitiligo suggested by genetic studies. The pattern of immunohistochemical expression suggests that vitiligo might be an epithelial disease and not just a melanocyte disorder.

Pilot-study of photodamaged skin and melasma using reflectance confocal microscopy

Introduction: Photoaging and melasma are frequent dermatological complaints. Confocal reflectance microscopy (CRM) is a recent technique that can be used for diagnostic evaluation of these dermatoses. Objectives: To evaluate the characteristics of the epidermis and dermis containing pigmentary alterations caused by photodamage and melasma with the assistance of CRM, and compare the findings linked to these changes with the perilesional region. Methods: A pilot study was conducted with eight female individuals (aged 38 to 50 years, Fitzpatrick phototypes from II to IV) with clinical diagnoses of photodamage (n = 4) and melasma (n = 4) in the facial malar region. The perilesional and lesional regions were compared regarding the thickness of the stratum corneum and viable epidermis, the depth of the interpapillary crests, and the presence of hyper-refractive structures. Results: The pigmentary alterations in the photodamaged skin revealed a morphological pattern — such as an increase in the depth of the interpapillary ridges in the lesion region — typical of solar lentigo. In the lesional region of volunteers bearing melasma, it was possible to observe the presence of dendritic cells in the epidermis and melanophages in the dermis. All volunteers had hyper-refractive keratinocytes in the lesional epidermis region. Conclusions: Considering the number of patients evaluated, it was possible to characterize and compare cutaneous pigmentary alterations caused by photodamage to those cause by melasma.

Tumores epidérmicos

The main carcinomas arising from the epidermis and the principle premalignant epidermal lesions are described. The major risk factor for all these lesions is solar ultraviolet radiation. Premalignant lesions are actinic keratosis (AK) which can transform into invasive lesions over time, and therefore must be treated either using destructive methods or with topical treatment. Malignant tumours arising in the epidermis include basal cell carcinoma (BBC) and epidermoid carcinoma (EC). BBC is the most common skin tumour. It does not usually cause distant metastases, but it is locally destructive. EC does carry the risk of systemic spread and metastasis in internal organs. In both cases, the treatment of choice is surgical removal. Other procedures can be used if surgery is contraindicated, such as radiotherapy or topical treatments.

Genome-Wide DNA Methylation Profiling Identifies Differential Methylation in Uninvolved Psoriatic Epidermis

Psoriasis is a chronic inflammatory skin disease with both local and systemic components. Genome-wide approaches have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one-third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability. Epigenetic modifications have been linked to psoriasis and altered DNA methylation patterns in psoriatic versus healthy skin have been reported in whole-skin biopsies. In this study, focusing on epigenetic modifications in the psoriatic uninvolved skin, we compared the lesional and non-lesional epidermis from psoriasis patients with epidermis from healthy controls. We performed an exhaustive genome-wide DNA methylation profiling using reduced representation bisulfite sequencing, which interrogates the methylation status of approximately 3-4 million CpG sites. More than 2,000 strongly differentially methylated sites were identified and a striking overrepresentation of the Wnt and cadherin pathways among the differentially methylated sites was found. In particular, we observe a strong differential methylation in several psoriasis candidate genes. A substantial number of differentially methylated sites present in the uninvolved versus healthy epidermis suggests the presence of a pre-psoriatic state in the clinically healthy skin type. Our exploratory study represents a starting point for identifying biomarkers for psoriasis-prone skin before disease onset.

Case of thymoma-associated cutaneous graft-versus-host disease-like disease successfully improved by narrowband ultraviolet B phototherapy.

Thymoma-associated graft-versus-host disease (GVHD)-like disease is a rare paraneoplastic disease seen in patients with thymoma. Here, we describe the first case of thymoma-associated GVHD-like disease localized to the skin that was successfully improved by a combination of systemic corticosteroids and whole-body narrowband ultraviolet (UV)-B phototherapy. The patient had developed toxic epidermal necrolysis-like erosive skin lesions over the whole body. Although systemic corticosteroids were effective up to a point, we were unable to begin the steroid taper. The addition of systemic narrowband UV-B phototherapy improved the skin manifestation of this disease, allowing corticosteroids to be reduced to a third of the original dose. Histopathologically, it was confirmed that the proportion of Foxp3-positive lymphocytes in the skin increased after narrowband UV-B irradiation. We propose that whole-body narrowband UV-B phototherapy is a good therapeutic option for the skin manifestation of thymoma-associated GVHD-like disease.

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

Poxviruses are large DNA viruses with varying zoonotic potential, and are recognised in a broad range of wildlife. Although poxviruses have been detected in kangaroos, their genetic relationships to poxviruses in other animals and humans is not well understood. Here, we present a novel genome sequence of a marsupial poxvirus, the Eastern grey kangaroopox virus (EKPV-NSW), isolated from a wild eastern grey kangaroo. In the present study, histopathologically confirmed epidermal pox lesions were used to recover the full-length viral genome and perform electron microscopic analysis, with both immature virions and intracellular mature virions detected. Subsequent analysis of the EKPV-NSW genome demonstrated the highest degree of sequence similarity with EKPV-SC strain (91.51%), followed by WKPV-WA (87.93%), and MOCV1 (44.05%). The novel EKPV-NSW complete genome encompasses most of the chordopoxviruses protein coding genes (138) that are required for genome replication and expression, with only three essential protein coding genes being absent. The novel EKPV-NSW is missing 28 predicted genes compared to the recently isolated EKPV-SC, and carries 21 additional unique genes, encoding unknown proteins. Phylogenetic and recombination analyses showed EKPV-NSW to be the distinct available candidate genome of chordopoxviruses.

Role of chemokines and the corresponding receptors in vitiligo: A pilot study.

To determine the levels and sources of chemokines in the serum and epidermis of vitiligo patients, we examined 80 active patients, 80 stable patients and 40 healthy controls. First, the serum levels of candidate chemokines were measured by Luminex assay, and levels of CCR5, CXCR1 and CXCR3 were measured in peripheral mononuclear cells (PMBC) by flow cytometry. Then, the local epidermis levels of elevated chemokines in vitiligo were tested by Luminex. Finally, the mRNA and protein expression levels of elevated chemokines in HaCaT cells stimulated with interferon (IFN)-γ or tumor necrosis factor (TNF)-α were tested by quantitative real-time polymerase chain reaction and Luminex. The serum levels of CCL5, CXCL8 and CXCL10 in active vitiligo were significantly elevated compared with those in stable vitiligo patients. Furthermore, the levels of CCL3 and CCL4 had weak and positive correlations with the Vitiligo Area Scoring Index. In the peripheral blood of active vitiligo patients, the percentages of CD3+ CD8+ CCR5+ and CD3+ CD8+ CXCR3+ T cells were significantly increased compared with those in stable vitiligo and healthy controls. In the epidermis of lesions, the expression levels of CCL5 and CXCL10 in active vitiligo were significantly increased. In addition, the mRNA and protein levels of CCL5, CXCL8 and CXCL10 were significantly elevated in HaCaT cells after stimulation with TNF-α or IFN-γ. The CCR5/CCL5 and CXCR3/CXCL10 axes may play an important role in the progression and maintenance of vitiligo. Moreover, keratinocytes stimulated with TNF-α and IFN-γ may be a primary source of CCL5 and CXCL10.

405 STAT3 activation causes IL-33 expression in normal human epidermal keratinocyte

Psoriasis is a chronic inflammatory skin disease which involves many cytokines such as TNF-α and IL-17A, with activated STAT3 in the lesional epidermis. IL-33 is a member of IL-1 cytokine family, which induces the production of type 2-associated cytokines from many immune cells, such as Th2 cells, ILC2, mast cells and eosinophils. Serum IL-33 levels in psoriasis patients were elevated compared to that in healthy donors. IL-33 was positive in the nucleus of lesional skin keratinocyte of psoriasis patients. We previously reported that IFN-γ and IL-17A induced IL-33 in normal human epidermal keratinocytes (NHEKs), which was dependent on activation of STAT1. In this study, we investigated the involvement of STAT3 in the induction of IL-33 in NHEKs. Oncostatin M (OSM) as well as IL-6 is a strong inducer of STAT3 activation. OSM and IL-6 induced IL-33 both at mRNA and protein levels in time- and dose-dependent manner, which was suppressed by JAK3 inhibitor and dominant negative STAT3. IL-33 expression induced by OSM was suppressed by TNF-α, while NFκ-B inhibitors, BAY11-7085 or SN50, did not affect the expression of IL-33 stimulated by OSM either at mRNA or protein level. We have identified three distinct promoter regions of IL-33. OSM and IFN-γ induced activity from the identical promoter of IL-33. We concluded that STAT3 is one of the major transcription factors which is involved in the induction of IL-33.

Mapping architectural and transcriptional alterations in non-lesional and lesional epidermis in vitiligo

In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis presents a challenge for long-term tissue maintenance. The stable vitiligo patches are known to attain an irreversible depigmented state. However, the molecular and cellular processes resulting in this remodeled tissue homeostasis is unclear. To investigate the complex interplay of inductive signals and cell intrinsic factors that support the new acquired state, we compared the matched lesional and non-lesional epidermis obtained from stable non-segmental vitiligo subjects. Hierarchical clustering of genome-wide expression of transcripts surprisingly segregated lesional and non-lesional samples in two distinct clades, despite the apparent heterogeneity in the lesions of different vitiligo subjects. Pathway enrichment showed the expected downregulation of melanogenic pathway and a significant downregulation of cornification and keratinocyte differentiation processes. These perturbations could indeed be recapitulated in the lesional epidermal tissue, including blunting of rete-ridges, thickening of stratum corneum and increase in the size of corneocytes. In addition, we identify marked increase in the putrescine levels due to the elevated expression of spermine/spermidine acetyl transferase. Our study provides insights into the intrinsic self-renewing ability of damaged lesional tissue to restore epidermal functionality in vitiligo.

TCR+ CD3+ CD4− CD8− effector T cells in psoriasis

The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR+CD3+CD4−CD8− “double negative” (DN) T cells can derive from CD8+ T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive.We demonstrate that a majority of DN T cells exhibits effector memory phenotypes, express IFN-γ, and fail to proliferate. DN T cells from psoriasis patients are characterized by reduced DNA methylation of the IFNG gene and increased PD-1 expression. Furthermore, PD-1 positive DN T cells infiltrate the epidermis in psoriatic skin lesions. Our observations offer additional insight into the molecular pathophysiology of plaque psoriasis and show promise as potential disease biomarkers and/or therapeutic targets for future interventions.

Systemic immune mechanisms in atopic dermatitis and psoriasis with implications for treatment.

Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases that negatively affect patients' quality of life. Although distinctions exist between these diseases, both are characterized by erythematous, thickened epidermal lesions that vary in intensity and affected body surface area. Early models of aetiology attributed symptoms of both diseases to cutaneous inflammation at lesion sites, but recent studies have established that activated immune mediators in the circulation drive disease severity. Activation of T helper 2 (Th2) and Th22 cells in the circulation appears to be the principal initiator of acute AD pathology, with the emergence of Th1 and Th17/interleukin (IL)-23 pathway activation marking the transition to a chronic state. The Th17/IL-23 pathway also has an important role in psoriasis. The role of systemic inflammation in AD and psoriasis is supported by the occurrence of non-cutaneous comorbidities that affect patients, most of which intensify morbidity and disability associated with lesional skin. Atopic dermatitis is associated with allergic disorders consisting of the "atopic march," whereas psoriasis is frequently accompanied by psoriatic arthritis. Patients with both disorders are at significantly higher risk of obesity, metabolic disorders, and cardiovascular diseases, all of which feature inflammatory components in their pathology models. These insights have led to novel therapeutics aimed at addressing psoriasis by targeting tumor necrosis factor- and Th17-related cytokine pathways. The success of these agents in psoriasis management is driving new therapeutic approaches for moderate-to-severe AD, including agents targeting the Th2 and Th17/Th22 cytokine pathways.

The caspase-1 inhibitor CARD18 is specifically expressed during late differentiation of keratinocytes and its expression is lost in lichen planus

BackgroundCARD18 contains a caspase recruitment domain (CARD) via which it binds to caspase-1 and thereby inhibits caspase-1-mediated activation of the pro-inflammatory cytokine interleukin (IL)-1β. ObjectivesTo determine the expression profile and the role of CARD18 during differentiation of keratinocytes and to compare the expression of CARD18 in normal skin and in inflammatory skin diseases. MethodsHuman keratinocytes were induced to differentiate in monolayer and in 3D skin equivalent cultures. In some experiments, CARD18-specific siRNAs were used to knock down expression of CARD18. CARD18 mRNA levels were determined by quantitative real-time PCR, and CARD18 protein was detected by Western blot and immunofluorescence analyses. In situ expression was analyzed in skin biopsies obtained from healthy donors and patients with psoriasis and lichen planus. ResultsCARD18 mRNA was expressed in the epidermis at more than 100-fold higher levels than in any other human tissue. Within the epidermis, CARD18 was specifically expressed in the granular layer. In vitro CARD18 was strongly upregulated at both mRNA and protein levels in keratinocytes undergoing terminal differentiation. In skin equivalent cultures the expression of CARD18 was efficiently suppressed by siRNAs without impairing stratum corneum formation. Epidermal expression of CARD18 was increased after ultraviolet (UV)B irradiation of skin explants. In skin biopsies of patients with psoriasis no consistent regulation of CARD18 expression was observed, however, in lesional epidermis of patients with lichen planus, CARD18 expression was either greatly diminished or entirely absent whereas in non-lesional areas expression was comparable to normal skin. ConclusionsOur results identify CARD18 as a differentiation-associated keratinocyte protein that is altered in abundance by UV stress. Its downregulation in lichen planus indicates a potential role in inflammatory reactions of the epidermis in this disease.

Patient satisfaction and reported outcomes on the management of actinic keratosis.

Actinic keratosis (AK) is a common dermatologic condition in which hyperplastic epidermal lesions develop in response to excessive and chronic exposure to ultraviolet (UV) radiation. If left untreated, AK can progress to squamous cell carcinomas of the skin. Incidence is rising worldwide as a result of the progressive aging of populations and an increase in lifetime cumulative exposure to UV radiation. Currently, various treatment options exist, which range from topical medications to light-based therapies and procedural modalities. In this article, we will review the treatment options for AK with a focus on assessments of patient satisfaction with treatment.

Genetic alterations in seborrheic keratoses.

Seborrheic keratoses are common benign epidermal lesions that are associated with increased age and sun-exposure. Those lesions despite harboring multiple somatic alterations in contrast to malignant tumors appear to be genetically stable. In order to investigate and characterize the presence of recurrent mutations, we performed exome sequencing on DNA from one seborrheic keratosis lesion and corresponding blood cells from the same patients with follow up investigation of alterations identified by exome sequencing in 24 additional lesions from as many patients. In addition we investigated alterations in all lesions at specific genes loci that included FGFR3, PIK3CA, HRAS, BRAF, CDKN2A and TERT and DHPH3 promoters. The exome sequencing data indicated three mutations per Mb of the targeted sequence. The mutational pattern depicted typical UV signature with majority of alterations being C>T and CC>TT base changes at dipyrimidinic sites. The FGFR3 mutations were the most frequent, detected in 12 of 25 (48%) lesions, followed by the PIK3CA (32%), TERT promoter (24%) and DPH3 promoter mutations (24%). TERT promoter mutations associated with increased age and were present mainly in the lesions excised from head and neck. Three lesions also carried alterations in CDKN2A. FGFR3, TERT and DPH3 expression did not correlate with mutations in the respective genes and promoters; however, increased FGFR3 transcript levels were associated with increased FOXN1 levels, a suggested positive feedback loop that stalls malignant progression. Thus, in this study we report overall mutation rate through exome sequencing and show the most frequent mutations seborrheic keratosis.

Molecular and histological characterization of age spots.

Age spots, also called solar lentigines and lentigo senilis, are light brown to black pigmented lesions of various sizes that typically develop in chronically sun-exposed skin. It is well known that age spots are strongly related to chronic sun exposure and are associated with photodamage and an increased risk for skin cancer; however, the mechanisms underlying their development remain poorly understood. We used immunohistochemical analysis and microarray analysis to investigate the processes involved in their formation, focusing on specific markers associated with the functions and proliferation of melanocytes and keratinocytes. A total of 193 genes were differentially expressed in age spots, but melanocyte pigment genes were not among them. The increased expression of keratins 5 and 10, markers of basal and suprabasal keratinocytes, respectively, in age spots suggests that the increased proliferation of basal keratinocytes combined with the decreased turnover of suprabasal keratinocytes leads to the exaggerated formation of rete ridges in lesional epidermis which in turn disrupts the normal processing of melanin upwards from the basal layer. Based on our results, we propose a model for the development of age spots that explains the accumulation of melanin and the development of extensive rete ridges in those hyperpigmented lesions.

Immunohistopathological Study of c-FLIP Protein in Mycosis Fungoides

Background:Mycosis fungoides (MF) is the commonest variant of primary cutaneous T cell lymphoma with several clinicopathologic variants. Defective apoptotic mechanism may be important in the pathogenesis and progression of MF. c-FLIP protein is an important anti-apoptotic marker and chemotherapeutic resistant factor. This study aimed to evaluate the c-FLIP expression in MF and its role in the pathogenesis of MF.Methods:Twenty patients of MF and ten normal persons were included in this study. Skin biopsies were obtained from both patients and controls. They were studied and examined immunohistochemically for the expression of CD4 and c-FLIP.Results:c-FLIP expression was significantly increased in patients when compared to controls in both epidermis and dermis. There were positive correlations between c-FLIP expression and CD4+ expression in both epidermal and dermal lesions of patients group. There were statistically significant positive correlations between c-FLIP expression (in both dermal and epidermal lesions) and the age of patients. c-FLIP expression increased with the tumor progression but with no statistical significance.Conclusion:Defective regulation of apoptosis has been considered as a main cause for accumulation of clonal T cells, and it was related to an increased expression of c-FLIP which may have a role in the pathogenesis of MF. Also, c-FLIP may have prognostic information in MF as its level increased with both age of the patients and tumor progression.

ピコ秒レーザーによる刺青および良性色素性病変に対する治療

Since 2013, novel picosecond duration lasers (ps-lasers) have become commercially available and the subsequent clinical trials have reported the safety and efficacy in treating multicolored and recalcitrant tattoos. It is considered that irradiation of targets with the ultra-short picosecond pulses can induce almost instantaneous heating of chromophores in the skin and greater fragmentation of the targets in an almost nonlinear fashion, with even less damage to adjacent structures than was achieved with the ns-domain lasers. These laser-tissue interaction caused by picosecond duration laser irradiation is named photoacoustic or photomechanical effect, not photothermal effect.Application of the ps-laser for the treatment of unwanted tattoos was started in authors’ clinic from December 2013. From our experience of the great success of tattoo removal with the ps-laser, we have also started the treatment of epidermal or dermal benign pigmented lesions with ps-lasers, and have obtained good clinical results without persistent adverse effects such as post-inflammatory hyper-pigmentation, hypo-pigmentation and scarring.These novel laser devices, which have been developed based on the theory of ps-laser tissue interaction, might set the fashion for the new approach to treat the cutaneous pigmented lesions.