Acquired dermal macular hyperpigmentation (ADMH) is a group of diseases clinically characterized by grayish-black macules and patches, with pigment predominantly deposited in the dermis. ADMH includes Riehl's melanosis, lichen planus pigmentosus, and erythema dyschromicum perstans/ashy dermatosis. In light of the remarkable similarities in both morphological and histopathological characteristics among this group of diseases, the academic community has recently proposed the new nosological term "acquired dermal macular hyperpigmentation" to achieve integration and unified classification of these related disorders. This review comprehensively elaborates on advances in the diagnosis and treatment of ADMH, including clinical manifestations, dermoscopic findings, pathological characteristics, and treatment progress.

Objective:To determine the genetic causes of dystonic cerebral palsy (DCP) of unknown etiology by using whole exome and mitochondrial gene detection methods, and to analyze clues for early identification of DCP.Methods:This was a retrospective analysis of clinical data describing 21 children with unknown etiology and DCP-like phenotypes. It involved collecting a detailed medical history, biochemical testing, neuroimaging, electroencephalography and hematuria metabolic screening. Peripheral blood was collected from the children, their parents and their siblings. Genomic DNA was extracted, and whole exome and/or mitochondrial gene sequencing was performed to obtain variant sites and annotations. The candidate variants were verified by Sanger sequencing.Results:No clear perinatal risk factors were found in the 21 cases, though there was 1 case of family history. Laboratory tests found increased lactic acid in 3 and abnormal thyroid function in 2 cases. The neuroimaging showed lesions in the basal ganglia in 2 cases, delayed myelination in 6 cases, sometimes with cortical dysplasia, a wide extracerebral space and/or a thin corpus callosum. The images of 11 of the children were normal. Later follow-up showed changes in the brain magnetic resonance images (MRIs) of 2 of the children. Pathogenic or likely pathogenic candidate variants were identified in 15 of the 21 children (71%) within 12 genes: TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MT- ATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 or NACC1. Fifteen of the children received a precise diagnosis. Genetic testing found heterozygous variants of ATP1 A2, SPR, ATP1 A3, MED13 L or NR4 A2 genes in the remaining six children, all of which were non-pathogenic variants. Conclusions:The absence of perinatal high-risk factors, a positive family history, and a normal or progressive brain MRI can be used as early clues to identify atypical DCP cases. TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MTATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 and NACC1 variants belong to the spectrum of DCP-related pathogenic genes, and attention should be paid to the interpretation of genomic analysis results.

Objective:To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities.Methods:A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index (MASI) scores were calculated, and ΔMASI scores (baseline MASI scores - post-treatment MASI scores) were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results:A total of 254 patients (including 249 females, 98.0%) with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 (83.9%) patients, and Ⅳ in 41 (16.1%) patients; 180 (70.9%) patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition, 166 cases (65.4%) were classified as epidermal type, and 88 (34.6%) as mixed type. Pigmented lesions were located on the cheek (174 cases, 68.5%), midface (26 cases, 10.2%), or lower jaw (54 cases, 21.3%), with periorbital involvement observed in 127 cases (50.0%). Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group (19.75 ± 5.08) than in the skin type Ⅲ group (14.47 ± 4.18, P < 0.001), in the non-sunscreen users (16.45 ± 4.61) than in the sunscreen users (12.59 ± 3.91, P < 0.001), in the epidermal type group (15.99 ± 4.82) than in the mixed type group (14.07 ± 4.35, P < 0.001), in the mandibular type group (18.37 ± 5.14) than in the midfacial type group (14.23 ± 3.46, P < 0.001) and malar type group (14.54 ± 4.40, P < 0.001), as well as in the patients with periorbital involvement (16.54 ± 4.90) than in those without (14.10 ± 4.26, P < 0.001). According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group (109 cases, topically treated with 2% hydroquinone cream nightly), topical non-hydroquinone skin-lightening agents group (36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents), oral tranexamic acid group (50 cases, treated with oral tranexamic acid 250 mg twice daily), and alpha hydroxy acid (AHA) chemical peeling group (30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%). After treatment, MASI scores were significantly reduced from baseline in all the 4 groups (all P < 0.001), and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group (1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001). The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group (all P < 0.05), while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group ( P > 0.05). After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group (β = 2.64) and AHA chemical peeling group (β = 1.55) still showed significantly superior efficacy compared to the topical 2% hydroquinone group (both P < 0.05) ; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group (β = 1.87, P < 0.001) . Conclusions:Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Objective:To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities.Methods:A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index (MASI) scores were calculated, and ΔMASI scores (baseline MASI scores - post-treatment MASI scores) were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results:A total of 254 patients (including 249 females, 98.0%) with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 (83.9%) patients, and Ⅳ in 41 (16.1%) patients; 180 (70.9%) patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition, 166 cases (65.4%) were classified as epidermal type, and 88 (34.6%) as mixed type. Pigmented lesions were located on the cheek (174 cases, 68.5%), midface (26 cases, 10.2%), or lower jaw (54 cases, 21.3%), with periorbital involvement observed in 127 cases (50.0%). Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group (19.75 ± 5.08) than in the skin type Ⅲ group (14.47 ± 4.18, P < 0.001), in the non-sunscreen users (16.45 ± 4.61) than in the sunscreen users (12.59 ± 3.91, P < 0.001), in the epidermal type group (15.99 ± 4.82) than in the mixed type group (14.07 ± 4.35, P < 0.001), in the mandibular type group (18.37 ± 5.14) than in the midfacial type group (14.23 ± 3.46, P < 0.001) and malar type group (14.54 ± 4.40, P < 0.001), as well as in the patients with periorbital involvement (16.54 ± 4.90) than in those without (14.10 ± 4.26, P < 0.001). According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group (109 cases, topically treated with 2% hydroquinone cream nightly), topical non-hydroquinone skin-lightening agents group (36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents), oral tranexamic acid group (50 cases, treated with oral tranexamic acid 250 mg twice daily), and alpha hydroxy acid (AHA) chemical peeling group (30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%). After treatment, MASI scores were significantly reduced from baseline in all the 4 groups (all P < 0.001), and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group (1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001). The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group (all P < 0.05), while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group ( P > 0.05). After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group (β = 2.64) and AHA chemical peeling group (β = 1.55) still showed significantly superior efficacy compared to the topical 2% hydroquinone group (both P < 0.05) ; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group (β = 1.87, P < 0.001) . Conclusions:Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Acquired dermal macular hyperpigmentation (ADMH) is a group of diseases clinically characterized by grayish-black macules and patches, with pigment predominantly deposited in the dermis. ADMH includes Riehl's melanosis, lichen planus pigmentosus, and erythema dyschromicum perstans/ashy dermatosis. In light of the remarkable similarities in both morphological and histopathological characteristics among this group of diseases, the academic community has recently proposed the new nosological term "acquired dermal macular hyperpigmentation" to achieve integration and unified classification of these related disorders. This review comprehensively elaborates on advances in the diagnosis and treatment of ADMH, including clinical manifestations, dermoscopic findings, pathological characteristics, and treatment progress.

Objective:To determine the genetic causes of dystonic cerebral palsy (DCP) of unknown etiology by using whole exome and mitochondrial gene detection methods, and to analyze clues for early identification of DCP.Methods:This was a retrospective analysis of clinical data describing 21 children with unknown etiology and DCP-like phenotypes. It involved collecting a detailed medical history, biochemical testing, neuroimaging, electroencephalography and hematuria metabolic screening. Peripheral blood was collected from the children, their parents and their siblings. Genomic DNA was extracted, and whole exome and/or mitochondrial gene sequencing was performed to obtain variant sites and annotations. The candidate variants were verified by Sanger sequencing.Results:No clear perinatal risk factors were found in the 21 cases, though there was 1 case of family history. Laboratory tests found increased lactic acid in 3 and abnormal thyroid function in 2 cases. The neuroimaging showed lesions in the basal ganglia in 2 cases, delayed myelination in 6 cases, sometimes with cortical dysplasia, a wide extracerebral space and/or a thin corpus callosum. The images of 11 of the children were normal. Later follow-up showed changes in the brain magnetic resonance images (MRIs) of 2 of the children. Pathogenic or likely pathogenic candidate variants were identified in 15 of the 21 children (71%) within 12 genes: TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MT- ATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 or NACC1. Fifteen of the children received a precise diagnosis. Genetic testing found heterozygous variants of ATP1 A2, SPR, ATP1 A3, MED13 L or NR4 A2 genes in the remaining six children, all of which were non-pathogenic variants. Conclusions:The absence of perinatal high-risk factors, a positive family history, and a normal or progressive brain MRI can be used as early clues to identify atypical DCP cases. TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MTATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 and NACC1 variants belong to the spectrum of DCP-related pathogenic genes, and attention should be paid to the interpretation of genomic analysis results.

Objective:To compare the clinical data and peripheral blood levels of CXC chemokine ligand (CXCL) 9 and CXCL10 between patients with progressive non-segmental vitiligo who were sensitive to systemic glucocorticoid treatment and those who were resistant, and to clarify key clinical factors influencing the sensitivity to systemic glucocorticoid treatment.Methods:From May 2021 to May 2023, a cohort of patients with progressive non-segmental vitiligo receiving systemic glucocorticoid treatment was established in Huashan Hospital, Fudan University. Clinical data and peripheral blood samples were prospectively collected from all enrolled patients. Standard treatment, i.e., intramuscular injections of 1 ml of compound betamethasone once a month, was administered. After 3-month treatment, the improvement of patients′ skin lesions was estimated, and the vitiligo area and severity index (VASI) score and the Vitiligo European Task Force assessment tool (VETFa) were used to evaluate the efficacy. Patients with VASI changes ≥ 0 and VETFa progression scores ≤ 0 point were included in the glucocorticoid-sensitive group (i.e., the patients′ condition was stable or improved), otherwise those with VASI changes < 0 and VETFa progression scores of 1 point were included in the glucocorticoid-resistant group. Associations of lesion locations, specific clinical markers (trichrome lesions, confetti-like depigmentation, and Koebner phenomenon), previous medication history, family history of vitiligo, etc. with the response to systemic glucocorticoid treatment were analyzed. At baseline and after 3-month treatment, peripheral blood samples were collected from the patients, and enzyme-linked immunosorbent assay was performed to detect the plasma levels of CXCL9 and CXCL10. Statistical analysis was carried out by using the chi-square test, Fisher′s exact test, binary logistic regression analysis, Mann-Whitney U test, and Wilcoxon signed-rank test. Results:A total of 142 patients with vitiligo were enrolled, and 127 completed 3-month treatment, including 77 males and 50 females. Their age at diagnosis was 18 to 65 (36.6 ± 11.4) years, and the disease duration ranged from 2 months to 58 (13.5 ± 10.7) years; 25 (19.7%) had a family history of vitiligo; the percentage of lesion area to total body surface area before treatment ranged from 1% to 70% (11.5% ± 12.7%), and the VASI score was 1% to 70% (10.8% ± 11.6%). Multivariate logistic regression analysis showed that the absence of specific clinical markers (odds ratio [ OR] = 6.900, 95% confidence interval [ CI]: 1.228, 38.757, P = 0.028), carrying a single specific clinical marker ( OR = 2.579, 95% CI: 1.012, 6.574, P = 0.047), having a history of topical glucocorticoid treatment ( OR = 2.643, 95% CI: 1.019, 6.850, P = 0.041), the absence of family history of vitiligo ( OR = 5.090, 95% CI: 1.070, 24.215, P = 0.030), and lesions on the proximal extremities ( OR = 3.767, 95% CI: 1.315, 10.793, P = 0.037) were risk factors for the resistance to systemic glucocorticoid treatment in the patients with vitiligo. After 3-month treatment, the glucocorticoid-sensitive group showed a significant decrease in plasma CXCL10 levels compared with those before treatment ( W = 571.00, P < 0.001), while there was no significant difference between the pre- and post-treatment CXCL10 levels in the glucocorticoid-resistant group ( W = 48.00, P = 0.524). Additionally, no significant difference was observed in changes of the plasma CXCL9 level before and after treatment between the glucocorticoid-sensitive and glucocorticoid-resistant groups ( P > 0.05) . Conclusions:Carrying no or a single specific clinical marker, having a history of topical glucocorticoid treatment, the absence of family history of vitiligo, and lesions on the proximal extremities appeared to be risk factors for the resistance to systemic glucocorticoid treatment in patients with progressive non-segmental vitiligo. Changes in CXCL10 levels after treatment may be used as an important evaluation indicator for determining whether patients with progressive vitiligo were resistant to systemic glucocorticoid treatment.

Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.

BACKGROUND: Vitiligo is a common acquired pigmentary disease caused by destruction of epidermal melanocytes in underlying autoimmune response. Few studies have been focused on the role of chemokines in non-segmental vitiligo (NSV) concomitant with autoimmune thyroid disease (AITD) and alopecia areata (AA). OBJECTIVE: The aim of this study was to determine the best serum biomarker for predictive role in the progression of vitiligo and to evaluate the influence of AA and/or AITD on vitiligo by using the biomarker. METHODS: This prospective cohort study recruited 45 NSV patients: 14 without either AITD or AA, 12 with AITD, 11 with AA, and 8 with both AITD and AA. Serum levels of CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL16 were analyzed by ELISA. CXCR3 mRNA expression was detected on PBMCs by RT-PCR. Improvement was evaluated using repigmentation scales. RESULTS: Serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with AITD or AA alone than in those without AITD or AA. Moreover, serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with both AITD and AA than in those with AITD or AA alone. Poorer repigmentation was observed in NSV patients with both AA and AITD than in those with AA or AITD alone. CONCLUSION: CXCL10 could be a biomarker to predict the progression of NSV. Dermatologists should pay much attention to those NSV patients concomitant with AITD and/or AA, for comorbidity might lead to more active autoimmune reaction.
Alopecia Areata ; Alopecia ; Autoimmunity ; Chemokine CXCL10 ; Chemokines ; Cohort Studies ; Comorbidity ; Enzyme-Linked Immunosorbent Assay ; Humans ; Melanocytes ; Prospective Studies ; RNA, Messenger ; Thyroid Diseases ; Thyroid Gland ; Vitiligo ; Weights and Measures

BACKGROUND: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial. OBJECTIVE: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management. METHODS: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted. RESULTS: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis. CONCLUSION: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.
Acute Generalized Exanthematous Pustulosis ; Adrenal Cortex Hormones ; Allopurinol ; Anti-Bacterial Agents ; Carbamazepine ; China ; Cicatrix ; Drug Hypersensitivity Syndrome ; Eosinophilia ; Humans ; Lymphatic Diseases ; Mortality ; Prognosis ; Public Health ; Retrospective Studies ; Skin ; Stevens-Johnson Syndrome ; Tertiary Healthcare