Etiology And Laser Treatment Of Café-au-lait Macules

Cafe-au-lait macules（CALMs）are clinically common pigmentation patches,with an incidence of 10-20%in the general population.It can be divided into single and multiple CALMs clinically,among which,single CALMs are common with the incidence of 2-3%in healthy newborns,with the increase of age,the incidence can even reach 1/3;that of multiple（three or more）CALMs is about 1%-14%.Generally speaking,solitary CALMs are common in the general population with no need of further examination.Multiple CALMs,which are rare and harmless,are often associated with a variety of genetic syndromes,such as neurofibromatosis,Legius syndrome et al.CALMs may be the first appearance which make the early diagnosis difficult.On the one hand,CALMs may be the early manifestation of serious hereditary systemic diseases,some of which are tumor susceptibility diseases.Early diagnosis is beneficial to follow-up and prognosis.On the other hand,CALMs are also present at a high rate in the normal population and may be harmless.Therefore,early detection of genetic screening is particularly important.On the one hand,mutation genes can be searched through gene sequencing,and the genetic causes of CALMs can be found from the molecular level,so as to provide genetic and molecular biological basis for clinical diagnosis and make accurate diagnosis for patients.On the other hand,the proven relationship between genotype and phenotype can guide the further monitoring of physical examination,especially the diagnosis at the pre-tumor stage,so as to provide appropriate guidance for the prognosis of many benign and malignant tumors,and provide family genetic counseling.CALMs is harmless in itself and generally will not go away.However,these brown macules can be cosmetically distressing to the patients,which will affect their learning and social interaction,and seriously affect their physical and mental health.Photoelectric therapy is a relatively effective treatment with relatively small side effects.However,the effect of laser therapy is random,in short,no laser can achieve a completely ideal therapeutic effect;the effectiveness of different laser therapy devices varies;the efficacy of the same laser varies in different reports.In different research results,the factors affecting the curative effect are different;different individuals or even different parts of the same lesions have unstable response to laser treatment.All the above are the key and difficult points in the current treatment.Based on the above research background,this study is mainly divided into the following two parts:Part 1:Genetic analysis of 11 patients with multiple Café-au-lait macules1.Objective:To explore the genetic etiology of patients with CALMs,so as to provide early diagnosis and intervention,and lay a foundation for prognosis,prenatal diagnosis and future gene therapy.2.Research methods:Under informed consent,5ml peripheral venous blood was extracted from 11 patients and some of their family members.After DNA extraction,DNA was sequenced for whole-genome exons.Specific primers were designed for sequencing results,and sanger sequencing method was used to verify the mutation patients,their family members and 100 normal controls.3.Results:A total of 11 patients were included in this study.The number and size of CALMs vary.All patients presented due to multiple CALMs.2 patients showed axillary and inguinal freckle.The growth and development of all the children were similar to those of the same age with normal intelligence.Two NF1 mutations were successfully detected as frame-shift mutations including C.4949dup and C.1756₁759del,and one of them met the clinical diagnostic criteria of The National Institutes of Health（NIH）for NF1.NF2 mutation was successfully detected in 1 patient which was splicing mutation C.240+15C>T.No mutation was detected in others.4.Conclusion:Through genetic testing of patients with CALMs,this study clarified the mechanism of partial CALMs from the molecular level,clarified the diagnosis,and pointed out the direction for disease monitoring and prognosis follow-up.Part 2:Clinical efficacy and safety analysis of Q-switch Nd:YAG laser in 440 patients of Cafe au lait Macules1.Objective:To retrospectively analyze the clinical effect of Q-switched Nd:YAG laser in the treatment of cafe-au-lait macules2.Methods:Patients with cafe-au-lait macules from 1999 to 2018,who received treatment in the laser cosmetology clinic of our hospital were analyzed.The entire treatment process used alone Q-switched 532nm or 1064nm or combined with sequential treatment,comparing the relationship between different variables such as gender,age of onset,age of treatment,course of disease,anatomic site,boundary,color,size,treatment wavelength and efficacy,and to determine whether there is statistical significance.3.Results:440 patients met the inclusion criteria.In terms of therapeutic effect,22 cases（5%）recovered,65 cases（14.8%）showed significant effect,18 cases（4.1%）were effective,114 cases（25.9%）improved,221 cases（50.2%）were ineffective,and the total effective rate was 49.8%.By statistical analysis we found that gender,age,disease treatment of age,course of the disease,anatomic site,lesion area and lesion boundaries,skin color,and treatment interval showed no statistically significant difference in clinical efficient.Clinical effective differs with different wavelength,which is statistically significant（chi-square:chi square=12.200,P=0.002）,compared with other two kinds of treatment of wavelength,wavelength of 532 patients with clinical effective rate is higher.The clinical efficacy of different treatment times was different,and the difference was statistically significant（χ2=13.104,P=0.022）.Clinical efficacy increased with the number of treatments（χ2=5.555,P=0.018）.4.Conclusion:Q-switched Nd:YAG laser is safe and effective in the treatment of Café au lait Macules,with few side effects.According to our research,532nm wavelength laser should be the first choice for treatment,and the treatment effect can be improved with more treatment.