[Genetic analysis of a child with Dyschromatosis symmetrica hereditaria].

OBJECTIVE: To investigate the clinical and genetic features of a child with Dyschromatosis symmetrica hereditaria (DSH) and variant of the ADAR1 gene. METHODS: A child who was admitted to the Department of Dermatology of the First Affiliated Hospital of Zhengzhou University in June 2020 due to irregular pigmented maculopapular rash on the dorsum of hands was selected as the study subject. Whole exome sequencing (WES) was carried out for the child and his similarly affected father, and Sanger sequencing was used to verify the candidate variant. SWISS-MODEL was used to predict the secondary and tertiary structures of the wild-type and mutant ADAR1 proteins. RESULTS: The child, a 13-year-old boy, had symmetrical hyperpigmented and depigmented spots on the back of his hands and was clinically diagnosed with DSH. WES and Sanger sequencing results showed that he and his father had both harbored a heterozygous c.2858dup (p.T954Dfs*20) truncating variant in exon 10 of the ADAR1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PM1+PP3). CONCLUSION: The c.2858dup (p.T954Dfs*20) variant of the ADAR1 gene probably underlay the DSH in this pedigree.

Excimer Laser Therapy for Pigmented Purpuric Dermatosis: A Case Study.

BACKGROUND Pigmented purpuric dermatosis (PPD) is a rare disease that is poorly understood but thought to result from inflammation of the capillaries causing extravasation of erythrocytes into the soft tissue. There are a variety of potential causes, including medications, such as acetaminophen and aspirin, abnormal humoral immunity, and excessive exercise. Although benign, PPD can be bothersome to patients due to associated pruritus, weeping, and poor cosmetic results. Treatment of this lesion is difficult, with no standardized regimen and a tendency for relapse once treatment is discontinued. CASE REPORT This case reports on a 77-year-old man who presented to an outpatient dermatology clinic with bilateral lower extremity edema with associated weeping and erythema for 1 year. A biopsy was conducted and resulted as PPD. He began treatment with excimer laser therapy after conservative and topical treatment options failed, with resolution of symptoms without recurrence for approximately 1 year. CONCLUSIONS PPD is notoriously difficult to treat, and historic treatment options include topical corticosteroids, oral supplements, and immunomodulators, all of which come with a range of adverse effects. However, new literature supports the use of phototherapy to treat PPD, with varying results. Previously implemented options include but are not limited to phototherapy with psoralen plus ultraviolet A, narrow band ultraviolet B, advanced fluorescence technology pulsed light, and fractional non-ablative 1540-nm erbium: glass laser, each with varying degrees of success. This case discusses the successful treatment of recalcitrant PPD with excimer laser therapy and maintenance of remission for approximately 1 year.

Management of the Sequelae of Skin Grafting: Pruritis, Folliculitis, Pigmentation Changes, and More.

Scars commonly give rise to unpredictable, potentially irritating, cutaneous complications including pruritis, folliculitis, and pigment changes. These problems can be self-limiting and are prevalent in many burn cases, although their expression varies among individuals. A better understanding of the presentation, risk factors, and pathophysiology of these long-term sequelae allows for more comprehensive care of burn survivors.

Therapeutic modulation of KIT ligand in melanocytic disorders with implications for mast cell diseases.

KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well-studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma.

[Analysis of ADAR gene variants in a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria in conjunct with developmental delay].

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria (DSH) in conjunct with developmental delay. METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University on May 28 2021 for abnormal skin pigmentation of the extremities and growth retardation for over 2 years was selected as the study subject. Clinical data of the child and his pedigree (11 individuals from three generations) was collected. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a two-year-and-seven-month-old male, had hyper- and hypopigmentation on his hands, feet and face, in addition with delayed development. All members of his pedigree had typical presentation of DSH. A heterozygous c.2657G>A variant was found in exon 8 of the ADAR gene in the child, his mother, and elder sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PM1+PM2_Supporting+PP1+PP3). CONCLUSION: The c.2657G>A variant of the ADAR gene probably underlay the DSH in this pedigree.

Using an intense pulsed light (IPL) module for the treatment of pigmented lesions.

BACKGROUND: Pigmented lesions are largely benign and may lead to extreme distress. Various light and lasers may be used to treat pigmentation, often Q-switched lasers are considered the method of choice, while intense pulsed light (IPL) devices may offer a less invasive treatment with a shorter downtime. OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of a narrowband IPL module for the treatment of pigmented lesions. METHODS: A retrospective study of 20 patients with pigmented lesions underwent treatment with an IPL module. Treatment was assessed by blinded evaluation of clinical photographs using a GAIS scale of 0-10, as well as through patient satisfaction ratings on a scale of 0-10. Throughout the treatment, pain levels and adverse events were monitored. RESULTS: The mean GAIS score was 7.55 ± 1.15 (mean ± SD), and the mean patient satisfaction score was 7.3 ± 1.26 (mean ± SD). There was a strong positive correlation between GAIS and patient satisfaction scores (r = 0.83), and no significant difference between them (p-value = 0.516). The number of treatments did not significantly affect GAIS and patient satisfaction scores (p-values 0.364 and 0.126). Additional positive unexpected outcomes were improved skin firmness and reduced wrinkles. CONCLUSION: The results of the study indicate that the IPL module is both safe and effective in treating pigmented lesions and may have the potential to stimulate collagen production.

Therapeutic Approach in Pigmented Purpuric Dermatoses-A Scoping Review.

Pigmented purpuric dermatoses (PPD) encompass a group of chronic skin conditions characterized by the presence of petechiae, purpura, and pigmentation changes. While generally benign, these dermatoses can be persistent and aesthetically bothersome. Key clinical features include red to brownish patches with a distinctive "cayenne pepper" appearance, predominantly localized on the lower extremities, particularly the shins. Subtypes include Schamberg disease, Majocchi's disease, Gougerot-Blum disease, Ducas and Kapetanakis pigmented purpura, and lichen aureus. Diagnosis relies primarily on clinical evaluation of skin lesions, with biopsy as a confirmatory tool. Although the exact cause of PPD remains unclear, capillary fragility and red blood cell extravasation are implicated. Treatment strategies for PPD aim to alleviate symptoms, considering the generally benign and chronic nature of the condition. As there is no standardized treatment, various methods with varying efficacy are employed. After searching SCOPUS and PubMed databases, we assessed 42 original articles to present current knowledge regarding therapy of PPD. This review will compare treatment approaches specifically in Schamberg disease and other manifestations of pigmented purpuric dermatoses.

The potential of facial nevi in personal identification.

Forensic anthropologists dealing with personal identification (PI) of human remains have recently stressed the need to explore the potential of "secondary identifiers" for identifying victims who died in particular events for whom images often represent the main antemortem data available. Being the face the part most exposed in images, characteristics as pigmented skin lesions (PSLs), can be crucial if combined with other input. Since no data is available on frequencies and distribution of facial PSLs in the general population, this study aims at systematically collecting such data to verify their potential in PI and to open a debate on the aid that "secondary identifiers", regardless of their specific nature, can give to the identification of the deceased in specific forensic contexts. A retrospective analysis on three-dimensional facial models of 1039 Italian subjects (from 4 to 84 years old) was conducted to examine the incidence of PSLs discriminated according to size and position in well-defined facial areas. From the collected data we developed a probabilistic approach providing the likelihood ratio (LR) for two settings: (1) the relative frequencies of nevi in the various facial areas, providing the deriving compound probability of owning a certain facial PSLs pattern; and (2) codes describing the facial nevi pattern of each individual of our population, thus testing their uniqueness and so their potential in PI. The calculated LRs mostly proved high identifying strength, particularly when provided by the compound probability-based approach. Data on incidence and position of facial nevi, their generated codes, and the probabilistic approach here presented, all constitute a starting point for advancing secondary identifiers. Nonetheless, although this preliminary study proved facial PSLs as valuable and potentially useful for identification, their significance and validity should be interpreted with caution as we are still at the first theoretical step clearly based on ideal conditions, and thus further investigations are due on the limitations of their use in practical identifying settings. Therefore, being this systematic study only a preliminary one in its nature, it is recommended not to use this kind of approach until further studies will test its validity in several practical conditions.

Investigation of the pathogenesis of ADAR1 gene in dyschromatosis symmetrica hereditaria.

The pathogenesis of dyschromatosis symmetrica hereditaria (DSH) has not been well defined. In this study, we sought to investigate the influence of the ADAR1 gene on DSH both in vitro and in vivo. Morpholino knockdown of adar1 in zebrafish produced phenotypes characterized by polarity changes, and abnormal migration and distribution of melanocytes. Differential expression of C-KIT and distinct patterns of apoptosis between hyperpigmented and hypopigmented areas in DSH patient were detected by means of immunohistochemical methods and TUNEL assays, respectively. This study revealed that adar1 knockdown in a zebrafish model resulted in abnormal migration and changes in the cell polarity of melanocytes, and provided novel insight into the mechanism of DSH pathogenesis.

Elastofibromatous changes in giant cell fibroma and amalgam tattoo: Unusual findings in common oral lesions.

Several cases of elastofibromatous lesion affecting the oral mucosa have been reported. Clinically, these lesions may appear as small exophytic lesions or less often as white lesions. Therefore, fibrous hyperplasia and leukoplakia are not uncommonly considered in clinical differential diagnosis. Microscopically, elastic and fibrous connective tissue deposition is seen. Rarely, elastofibromatous changes can be detected when assessing intraoral lesions, including cysts, salivary gland neoplasms, and epithelial dysplasia. Here we report two oral lesions showing elastofibromatous changes, expanding their clinicopathological spectrum. The first case was a 46-year-old man with a history of asymptomatic nodular lesion on the palate 1 year ago, diagnosed as giant cell fibroma with elastofibromatous changes. The second case was a 79-year-old woman who presented a pigmented and mildly symptomatic lesion on the mandibular alveolar mucosa several months ago, diagnosed as amalgam tattoo associated with elastofibromatous changes.

Glutathione amino acid precursors protect skin from UVB-induced damage and improve skin tone.

BACKGROUND: UV radiation exposure causes skin irritation, erythema, darkening and barrier disruption by inducing oxidative stress and inflammation. Glutathione, a master antioxidant, plays an important role in the antioxidant defence network of the skin. OBJECTIVE: This study aimed to assess the in vitro protective effects of the glutathione amino acid precursors blend (GAP) on transcriptomic and phenotypic endpoints against UVB-induced challenges. METHODS: Normal human epidermal melanocytes (NHEMs) were exposed to GAP, ascorbic acid (AA) and its derivatives. Viability was assessed using the CCK8 method. Melakutis®, a pigmented living skin equivalent (pLSE) model, underwent repeated 50 mJ/cm2 UVB irradiation with or without GAP treatment. Images of the model were captured with consistent camera parameters, and the model's light intensity was measured using a spectrophotometer. Melanin content was determined by measuring absorbance at 405 nm. Confirmation of melanin deposition and distribution was achieved through Fontana-Masson staining. Transcriptomic analysis was conducted using RNA sequencing (RNA-Seq), and a machine learning approach was employed for transcriptomic aging clock analysis. RESULTS: In NHEMs, all tested compounds exhibited over 85% viability compared to the vehicle control, indicating no heightened risk of cytotoxicity. Notably, GAP demonstrated greater efficacy in inhibiting melanin production than AA derivatives at equivalent concentrations. In pLSE models, GAP notably enhanced model lightness, and reduced melanin content and deposition following the UVB challenge, whereas AA showed minimal impact. GAP effectively counteracted UVB-induced alterations in gene expression linked to pigmentation, inflammation and aging. Moreover, recurrent UVB exposure substantially elevated the biological age of pLSE models, a phenomenon mitigated by GAP treatment. CONCLUSIONS: In NHEMs, GAP exhibited enhanced effectiveness in inhibiting melanin production at identical tested doses in comparison to AA derivatives. Noteworthy protective effects of GAP against UVB irradiation were observed in the pLSE models, as evidenced by skin pigmentation measurements and transcriptomic changes.

Shaken adult syndrome due to ocean wave: an autopsy case.

Severe intracranial trauma during torture or assault is reportedly caused by shaken adult syndrome. However, intracranial traumas caused by natural forces, excluding human factors and collision impact, are extremely rare. We report an autopsy case of shaken adult syndrome caused by ocean wave forces. A man in his 40s without any medical history was washed away by a wave during recreational fishing. He was found approximately 500 m away from the fishing point drifting on the ocean in a state of cardiopulmonary arrest and was confirmed dead, with no response to cardiopulmonary resuscitation, 3 h after the accident. The autopsy revealed no mechanical trauma to the entire body surface, including the head. Both lungs were inflated, and pleural effusion was observed. The brain was swollen and congested, and subarachnoid hemorrhage was observed in the interhemispheric fissure and the convexity of the parietal occipital lobe. Macroscopic and microscopic hemorrhage spots were found in the brain, and the results of the blood alcohol test and urinary toxicological screening were negative. The cause of death was determined as drowning. This case demonstrates a rare but notable mechanism of injury observed in immersed bodies.

A case of certolizumab-induced purpura annularis telangiectodes of Majocchi and literature review.

Tumor necrosis factor alpha (TNFα) inhibitors are now widely used to treat immune-mediated inflammatory diseases. Although they have a good safety profile, they are also associated with adverse cutaneous events. Pigmented purpuric dermatoses (PPD) include a variety of skin diseases characterized by multiple petechial hemorrhages due to capillaritis. Five major clinical types of PPD have been described and purpura annularis telangiectodes of Majocchi (PATM) is a rare subtype of PPD. The cause of PPD is unknown, but drugs are implicated in a minority of cases. There are very few cases in the literature triggered by TNFα inhibitors. We present a case of PATM induced by certolizumab pegol and perform a review including 4 articles in the literature reporting 5 PPD cases induced by TNFα inhibitors. When purpuric eruptions develop in patients treated with TNFα inhibitors, PPD and vasculitis should be differentiated. Thus, patients are not exposed to unnecessary evaluations and treatments.

Modeling of pigmentation disorders associated with MITF mutation in Waardenburg syndrome revealed an impaired melanogenesis pathway in iPS-derived melanocytes.

Waardenburg Syndrome (WS) is a rare genetic disorder that leads to congenital hearing loss and pigmentation defects. Microphthalmia-associated transcription factor (MITF) is one of its significant pathogenic genes. Despite the comprehensive investigation in animal models, the pathogenic mechanism is still poorly described in humans due to difficulties accessing embryonic tissues. In this work, we used induced pluripotent stem cells derived from a WS patient carrying a heterozygous mutation in the MITF gene c.626A>T (p.His209Leu), and differentiated toward melanocyte lineage, which is the most affected cell type involved in WS. Compared with the wild-type cell line, the MITFmut cell line showed a reduced expression of the characteristic melanocyte-related genes and a lesser proportion of mature, fully pigmented melanosomes. The transcriptome analysis also revealed widespread gene expression changes at the melanocyte stage in the MITFmut cell line. The differentially expressed genes were enriched in melanogenesis and cell proliferation-related pathways. Interestingly, ion transport-related genes also showed a significant difference in MITFmut -induced melanocytes, indicating that the MITF mutant may lead to the dysfunction of potassium channels and transporters produced by intermediate cells in the cochlea, further causing the associated phenotype of deafness. Altogether, our study provides valuable insights into how MITF mutation affects WS patients, which might result in defective melanocyte development and the related phenotype based on the patient-derived iPSC model.

Absent meibomian glands and cone dystrophy in ADULT syndrome: identification by whole exome sequencing of pathogenic variants in two causal genes TP63 and CNGB3.

BACKGROUND: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome. METHODS: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing. RESULTS: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases. CONCLUSIONS: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.

Dyschromatosis symmetrica hereditaria: A clue to early diagnosis of Aicardi-Goutières syndrome.

A 6-year-old female with a history of Aicardi-Goutières syndrome (AGS) presented to dermatology clinic with hypopigmented and hyperpigmented macules and patches consistent with dyschromatosis symmetrica hereditaria (DSH). Previous genetic workup demonstrated a de novo, heterozygous mutation in the adenosine deaminase acting on RNA 1 (ADAR) gene. While the co-occurrence of AGS and DSH has previously been described in mutations of the ADAR gene, our case highlights the potential association between these disorders that may aid in earlier future diagnosis of AGS.

Melanocyte colonization and pigmentation of breast carcinoma: A case report.

Pigmented mammary Paget disease is a rare variant of mammary Paget disease that is often clinically misdiagnosed as a melanocytic lesion of the skin or nipple-areolar complex. Careful morphological assessment, along with the performance of adequate immunohistochemical stains, will help in achieving the right diagnosis and avoiding misdiagnosis of the entity as malignant melanoma. We report a rare case of pigmented mammary Paget disease with concomitant colonization of the underlying invasive ductal carcinoma by melanocytes mimicking melanoma.

Pigment deposits in the retrolental space of Berger: a rare feature of pigment dispersion syndrome? / Depósitos de pigmento no espaço de Berger: uma característica rara de síndrome de dispersão pigmentar?

ABSTRACT Pigment dispersion syndrome is associated with clinical features such as Krukenberg's spindles, trabecular pigmentation, Scheie's stripe and Zentmayer's ring. Another less common feature of this syndrome is retrolental pigment deposits due to anterior hyaloid detachment or a defect in the Wieger's ligament. We present two cases of pigment deposits on the posterior lens capsule. In both cases, there is bilateral dispersion of pigment throughout the anterior segment. The retrolental deposits are unilateral in the first case and bilateral in the second. Both patients report a history of ocular trauma. This is a possible important clinical sign of pigment dispersion syndrome, rarely described.

RESUMO A síndrome de dispersão pigmentar associa-se a sinais clínicos característicos como fuso de Krukenberg, hiperpigmentação da malha trabecular, linha de Scheie e anel de Zentmeyer. Um sinal menos comum dessa síndrome é o depósito de pigmento posterior ao cristalino, que ocorre por um descolamento da hialoide anterior ou um defeito no ligamento de Wieger. Apresentamos dois casos de depósitos de pigmento posterior à cápsula posterior do cristalino. Em ambos os casos, existia dispersão bilateral de pigmento por todo o segmento anterior. No primeiro caso, os depósitos eram unilaterais e, no segundo, estavam presentes em ambos os olhos. Este pode corresponder a um sinal potencialmente importante da síndrome de dispersão pigmentar, raramente descrito.