C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse.

Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

Successful treatment of infantile refractory bullous pemphigoid with baricitinib.

Infantile bullous pemphigoid (BP) is a rare autoantibody-mediated skin disorder. We report the effective treatment of a 6-month-old infant with BP using baricitinib, a Janus kinase (JAK) inhibitor, after failure with steroids and intravenous immunoglobulin. The patient achieved full remission and discontinued all medications without any relapses. To our knowledge, this is the first case of baricitinib used in an infant with BP.

Validation of diagnostic criteria for atopic dermatitis and proposal of novel diagnostic criteria for adult and elderly Chinese populations: a multicentre, prospective, clinical setting-based study.

BACKGROUND: A previous validation study showed a very low sensitivity and higher specificity associated with Hanifin and Rajka criteria (H&R) and the UK Working Party criteria (UKWP) in diagnosing AD vs. the Chinese criteria of atopic dermatitis (AD) for children (CCAD). However, their diagnostic efficacy in adult and elderly Chinese populations remains unknown. OBJECTIVES: To validate the diagnostic efficacy of three sets of AD criteria in adult and elderly Chinese populations in a hospital setting. METHODS: A total of 1034 patients (aged 19-95 years) from five university hospital dermatological clinics were recruited. Medical history, dermatological examination, AD diagnosis and evaluation of AD severity were done by dermatologists. Each patient was investigated by two dermatologist panels, one to establish a clinical diagnosis, and the other to identify and record the major or minor signs of H&R criteria, UKWP criteria and CCAD. Taking clinical diagnosis as the reference, the diagnostic efficacy of three sets of diagnostic criteria was evaluated. The χ2 test or rank sum test were used for between-groups comparisons. RESULTS: CCAD had a higher sensitivity (84.0%), especially among mild and moderate cases of AD (72.7% and 90.3%, respectively), than the H&R (58.0%; P < 0.001) and UKWP criteria (56.0%; P < 0.001) in diagnosing AD. The specificity of CCAD (92.7%) was slightly lower than the H&R (97.3%; P < 0.001) or UKWP criteria (97.4%; P < 0.001). The CCAD had the highest Youden index (0.77), accuracy rate (0.90) and Kappa value (0.76) of the three sets of diagnostic criteria. CONCLUSIONS: Consistent with results in a population of Chinese children, although the H&R and UKWP criteria had a high specificity for diagnosing AD, their low sensitivity limited their use in adult and elderly Chinese patients. Based on the high sensitivity and favourable diagnostic efficacy, the CCAD is proposed for AD diagnosis in adult and elderly Chinese populations, especially for cases of mild and moderate AD.

Hyperpigmentation in an Elderly Patient with Atopic Dermatitis: A Quiz.

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Genotype and phenotype correlations in 441 patients with epidermolysis bullosa from China.

BACKGROUND: Epidermolysis bullosa (EB) is a heterogeneous group of rare and incurable genetic blistering disorders. OBJECTIVES: The objective was to analyse the genotype-phenotype correlation in EB among Chinese individuals. METHODS: Next-generation sequencing and Sanger sequencing were performed to genetically confirm clinically diagnosed EB. Reverse transcription-PCR and splice-site analysis were used to evaluate the consequences of splicing mutations. RESULTS: A total of 441 cases (413 families) across 11 genes were included. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, simplex and junctional compound EB accounted for 23.4%, 12.7%, 61.5%, 1.1% and 0.2%, respectively. In 16 probands with presumptive recessive EB, failed to find the second allele, COL7A1 (10), COL17A1 (4), LAMB3 (1) and ITGB4 (1). De novo mutations are common in dominant EB (63.8% in EBS, 27.5% in DEB) but extremely rare in recessive DEB (RDEB; 0.74%). Mosaicism is more common than presumed, with 5.4% of dominant EBS. In JEB, only 45.0% of patients with biallelic premature termination codon (PTC) mutations in laminin 332 genes died within 24 months, with a longer average survival age of 11.1 months. In JEB, unusual phenotypes are frequently observed, notably urinary tract involvement, duodenal atresia and EB nevi. In RDEB, 48.8% of cases with biallelic PTC mutations in COL7A1 exhibited a relatively mild phenotype; they are likely to develop a severe phenotype at 0-4 years old, and the PTC mutations position closer to the N-terminal, leading to earlier onset. Glycine substitution mutations in DEB have complex genotypic and phenotypic heterogeneity. The rare subtype, dominant and recessive compound DEB, consists of 1.8% of the total DEB. CONCLUSIONS: This study reveals the general rules governing genotype-phenotype correlations, rare phenotypes and complex genotypes. Collectively, mutation analysis in different forms of EB provides the basis for improved subclassification with accurate genetic counselling and for prenatal diagnosis.

The clinical efficacy and safety of anti-IgE therapy in recessive dystrophic epidermolysis bullosa.

The treatment of recessive dystrophic epidermolysis bullosa (RDEB) remains challenging. Elevated IgE levels have previously been reported in several RDEB patients. In this prospective, single-centre, open intervention study, elevated IgE levels were seen in 11 out of 12 patients with intense pruritus, and the patients with elevated IgE levels received anti-IgE therapy every 4 weeks for at least three cycles. Compared with the baseline, 10 patients with RDEB had good clinical outcomes with enhanced wound healing, a reduction in Birmingham (epidermolysis bullosa) EB severity score by 15%, a reduction in affected body surface area by 23.3%, amelioration of skin inflammation, and an increase in type VII collagen deposition by 13.1-fold. All the patients had a good tolerance to anti-IgE therapy. Furthermore, patients with higher IgE levels tended to have higher disease severity and more favorable clinical outcomes. Our report also suggested the potential role of IgE in the pathogenesis of inflammatory conditions associated with RDEB. (ChiCTR1900021437).

Detection and characterization of low-level mosaicism among clinically unaffected parents of 'sporadic' epidermolysis bullosa simplex cases.

In this study, two (18.2%) clinically unaffected parents from 11 trios were identified with mosaic KRT14 variants.To our knowledge, this is the first report to study the proportion of low-level mosaicism in the clinically unaffected parents whose children were previously regarded as sporadic EBS cases.

Centrifugal lipodystrophy on a spectrum with lupus erythematosus panniculitis in children and efficacy and safety of hydroxychloroquine: A clinicopathological study.

This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n = 24) and CLD/LEP overlap (n = 5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female = 1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n = 2), subcutaneous nodules (n = 2) and alopecia along Blaschko's lines (n = 1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p = 0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p > 0.99). HCQ (5 mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5 mg/kg/d) was effective and safe for treating CLD (age >1.5 years), and early treatment and a regular long-term follow-up are essential.

Intravenous immunoglobulin therapy in children with severe atopic dermatitis.

Children with severe atopic dermatitis (AD) can benefit from intravenous immunoglobulin (IVIG) therapy. This study aimed to identify the efficacy and safety of IVIG therapy in children with severe AD. Twenty pediatric AD patients were enrolled in this study. Patients with an Investigator's Global Assessment score of 0 or 1 or a reduction of 2 points after treatment were defined as high-responders (HRs), otherwise, they were defined as low-responders (LRs). Twelve patients (60%) achieved an excellent treatment response after 2 months, while eight (40%) had a low response. The Scoring Atopic Dermatitis index had improved significantly at 2 months post-treatment compared with baseline (p < 0.001). Baseline total serum IgE levels and eosinophil counts were elevated in all subjects and decreased significantly at 2 months post-treatment (p = 0.004 and 0.021, respectively). Baseline IgE levels were significantly higher in the HR group compared with the LR group (p = 0.020). The treatment was well tolerated. Fever was the most common adverse event and occurred in five patients (25%). In conclusion, IVIG could be a safe and effective therapy for children with severe AD and may be more effective in patients with higher IgE levels. Further studies are needed to investigate the different therapeutic responses in patients with different AD phenotypes.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Local Hyperthermia Versus Cryotherapy for Treatment of Plantar Warts: A Prospective Multi-centre Non-randomized Concurrent Controlled Clinical Trial.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

Comparison of the efficacy and safety between a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser and a conventional Q-switched 532-nm laser for the treatment of cafe-au-lait macules in 40 Chinese children: a prospective, randomized, parallel-controlled, evaluator-blinded trial.

Cafe-au-lait macules (CALMs) affect the appearance of patients and can result in serious psychological problems. Successful treatments without adverse effects remain challenging. We designed a prospective, randomized, controlled, evaluator-blinded trial on 40 pediatric patients to compare the efficacy between a low-fluence 1064-nm Q-switched Nd:YAG laser and a Q-switched Nd:YAG 532-nm laser for the treatment of solitary CALMs in children. We randomly assigned participants into 2 groups. We treated those in the first group with 3 sessions of 532-nm QS laser at 1-month intervals, and those in the second group with 6 sessions of 1064-nm LFQS laser at 2-week intervals. We found no significant differences in treatment efficacy (p = 0.14). The 1064-nm laser group referred significantly less pain than the 532-nm laser group (p = 0.0001). Side effects were detected in 5 patients in the 532-nm laser group. The difference of the side effects was statistically significant (p = 0.04). Two patients in 532-nm laser group were recurred and none in 1064-nm laser group. On a univariate logistic regression analysis, lesions with brown color, small size, and irregular edges were significantly associated with better outcomes (> 50% clearance). Multivariate logistic regression analysis found that brown lesions and lesions with irregular edges had higher odds of getting > 50% clearance (p < 0.05). In conclusion, the 1064-nm LFQS laser produced fewer side effects, less pain, and shorter recovery time than the 532-nm laser. Irregular-bordered, smaller, brown lesions improved better than smooth-bordered, larger, light brown lesions. Moreover, the 1064-nm laser may be a better choice for treating large size CALMs. However, no significant differences were found in terms of the treatment efficacy and recurrence.

Roles of Infection in Psoriasis.

Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations. Genetic predisposition, environmental factors, and immune dysfunction all contribute to the pathogenesis of psoriasis with host-microbe interaction governing the progression of this disease. Emerging evidence has indicated that infection is an environmental trigger for psoriasis and plays multiple roles in its maintenance as evidenced by the frequent association between guttate psoriasis onset and acute streptococcal infection. Different infectious factors act on immune cells to produce inflammatory cytokines that can induce or aggravate psoriasis. In addition to bacterial infections, viral and fungal infections have also been shown to be strongly associated with the onset or exacerbation of psoriasis. Intervention of skin microbiota to treat psoriasis has become a hot research topic. In this review, we summarize the effects of different infectious factors (bacteria, viruses, and fungi) on psoriasis, thereby providing insights into the manipulation of pathogens to allow for the identification of improved therapeutic options for the treatment of this condition.

Randomized clinical trial of combined therapy with oral α-lipoic acid and NB-UVB for nonsegmental stable vitiligo.

Vitiligo is associated with oxidant stress and α-lipoic acid (ALA) is an antioxidative agent. To evaluate the efficacy and safety of oral ALA in combination with NB-UVB phototherapy on nonsegmental stable vitiligo. The prospective, multi-center, parallel controlled, double-blind randomized clinical trial was conducted from 2012 to 2014, in seven comprehensive tertiary hospitals in China. The patients were randomized into oral ALA group or placebo group at a dose of 300 mg daily for 6 months. All of them received NB-UVB phototherapy three times weekly. The repigmentation rate was evaluated by 4-point grading scale of improvement: >98%, 50-98%, 10-49%, <10%. A total of 133 patients were enrolled in the study, including 72 cases in treatment group and 61 cases in control group. In treatment group, 2.04% (1/49) patients achieved ≥50% improvement at 1-month after enrollment (M1), and the percentage of patients increased to 8.51% (4/47), 14.0% (6/43), and 37.8% (14/37) at M2, M3, and M6, respectively. In control group, the percentages were similar at all timepoints. No significant difference was seen between the two groups (P > .05). For elder patients, younger patients, male or female, no significant differences were found between treatment group and control group at all timepoints. ALA did not show additional benefit to NB-UVB therapy in the treatment of nonsegmental stable vitiligo. More studies should be done to identify other protocols of ALA or other types of antioxidants for stable vitiligo.

Effect of Gentamicin Ointment in Patients with Nagashima-type Palmoplantar Keratosis: A Double-blind Vehicle-controlled Study.

Gentamicin ointment has potential in the treatment of Nagashima-type palmoplantar keratosis. However, there is a lack of reliable study data. The aim of this study was to perform a prospective, randomized, double-blinded, contralateral, vehicle-controlled clinical trial. A total of 20 subjects diagnosed with Nagashima-type palmoplantar keratosis by genetic test, who carried nonsense mutations, enrolled in the 30-day study. Gentamicin ointment was applied to the hand and foot on one side of the body, and vehicle ointment was applied to the hand and foot on the other side. The choice of hand and foot in each subject was randomly allocated. The severity of the patient's skin lesions and quality of life were assessed by a blinded evaluator, using the Dermatology Life Quality Index, visual analogue scale scores and digital photography. Gentamicin ointment treatment resulted in a significant improvement in symptoms of hyperkeratosis and foul smell compared with vehicle. No difference was found in the effect on erythema between gentamicin and vehicle. In conclusion, gentamicin ointment demonstrated positive responses and good tolerance in treating Nagashima-type palmoplantar keratosis caused by nonsense mutations.

Next-generation sequencing through multi-gene panel testing for diagnosis of hereditary ichthyosis in Chinese.

Inherited ichthyoses are a heterogeneous group of rare disorders related to over 40 genes. To identify underlying molecular causes in inherited ichthyosis among Chinese and to correlate genotype and phenotype, 35 probands clinically diagnosed inherited ichthyosis, except ichthyosis vulgaris and X-linked ichthyosis, were included in our study. Molecular analysis was performed using next-generation sequencing (NGS) through multi-gene panel testing targeting all ichthyosis-related genes. Genetic variants causative for the ichthyosis were identified in 32 of 35 investigated patients. In all, 43 causative mutations across 12 genes were disclosed, including 16 novel variants. Thirteen keratinopathic ichthyosis, fourteen autosomal recessive congenital ichthyosis (ARCI) including one caused by mutations in SDR9C7, and five syndromic ichthyoses were confirmed. Four probands, with presumptive ARCI, turned out to be keratinopathic ichthyosis (2), neutral lipid storage disease (1), and Sjogren-Larsson syndrome (1), respectively. Next-generation technology has been demonstrated to be an effective tool in diagnosing inherited ichthyosis constituting a diverse group of cornification disorders. Our study further expands mutation spectrum and clinical phenotype associated with inherited ichthyosis in Chinese.

Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population.

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.

Consensus of Chinese experts on protection of skin and mucous membrane barrier for health-care workers fighting against coronavirus disease 2019.

Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand-cleaning- and medical-glove-related hand protection, mask- and goggles-related face protection, UV-related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.