Amyloidosis Cutis Dyschromica—Dermoscopy,Reflection Confocal Microscopy Combined With Genetic Analysis

BackgroundAmyloidosis cutis dyschromica（ACD）is a rare subtype of primary localized cutaneous amyloidosis（PLCA）with an autosomal recessive inheritance pattern and the causative gene is GPNMB.Typical rashes are diffuse and symmetrically distributed hyperpigmentation and hypopigmented spots,with or without mild itching,and the disease progresses slowly,causing a certain social and psychological burden to patients.The detection of amyloid deposition in the superficial dermis of tissue biopsy can confirm the diagnosis of this disease,but it is difficult to repeat sampling of tissue biopsy.It is necessary to improve the clinical diagnosis of ACD through non-invasive examination methods.Objective1.In a Chinese Han family with ACD,the skin imaging analysis was provided by dermoscopy and skin reflection confocal microscopy（RCM）examination,and diagnosis was confirmed by histopathological.2.The GPNMB gene mutations were screened to expand the ACD genetic mutation spectrum;Literatures were reviewed to analyze the genotype-phenotype and histopathological characteristics of ACD,and provide reference for clinical diagnosis and treatment.Methods1.A Chinese Han family with ACD were collected.Skin lesions were analyzed by dermatoscopy and RCM,and confirmed by histopathological examination.Clinical data were collected and summarized.2.GPNMB were screened using Sanger sequencing.Bioinformatics analysis of mutations was performed using ANNOVAR software,and statistical data were processed by SPSS23.0 software.3.The published literature in the PubMed,CNKI,and CBM database were reviewed.Clinical characteristics and gene mutations of ACD were summarized,and genotype-phenotype analysis was performed.Results1.Under dermoscopy,ACD presents as patchy white hypopigmentation surrounded by brown spots,streaky hyperpigmentation,and large brownish hyperpigmented patches consisting of brown spots,interspersed with white reticulated hypopigmented patches.2.Genetic sequencing identified two genetic mutations on GPNMB: a missense mutation c.393T>G（p.Y131X;NM＿001005340）and a frameshift deletion mutation c.719＿720del TG（p.V240fs;NM＿001005340）.3.（1）ACD mostly occurs before or during adolescence.The average age of onset of familial ACD is 10±5 years old,and the average age of onset in sporadic cases is15±12 years old.（2）Among the 70 ACD patients,there were 37 males（52.9%）and 33females（47.1%）,and there was no significant gender difference in prevalence.（3）A total of 16 ACD-related protein changes were found,all of which were GPNMB gene mutations.c.565 C > T is a common mutation in ACD,and the related phenotype is complex.（4）In addition to the main manifestations of hyperpigmentation and hypopigmentation,some rare conditions such as blisters,erythema and epidermolysis may also occur in ACD.Conclusion1.The ACD features of dermoscopy and RCM were reported together for the first time,which provided a certain basis for the early non-invasive diagnosis and identification of the disease.2.The GPNMB gene in a Chinese Han ACD family was detected,two GPNMB mutation sites were found[c.393 T > G（p.Y131X;NM＿001005340）and c.719＿720del TG（p.V240fs;NM＿001005340）],and reference for genetic counseling of ACD was provided.3.Analyzing the published ACD cases,the rare phenotypes（vesicles,lichenification,epidermolysis）were summarized,genotype-phenotype analysis was conducted to improve clinicians’ understanding of the disease.