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We observed a remarkable response to spesolimab with an almost resolution of pustules in 12 h in one patient (Figure 1), two patients achieved resolution of pustules in 24 h, one patient is in 48 h, one patient is in 96 h. It is important to point out that PV lesions appeared in two out of the five patients (patient 3 and patient 4) during the observation period after the resolution of pustules. Patient 3 was treated with acitretin 30 mg twice daily orally and patient 4 treated with methotrexate 10 mg once weekly orally to treat the PV lesions after 4 weeks of spesolimab therapy. [Extracted from the article]

Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10−9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future. Author summary: Leprosy as a chronic infectious disease that affects the skin and nervous system is treated with a treatment cocktail, including rifampicin, clofazimine and dapsone. Unfortunately, one of these drugs, namely dapsone, may cause the patient to exhibit adverse symptoms that appear as skin hypersensitivity and may potentially lead to death up to 9.9% of the time. In a previous study, it has been established that this adverse drug reaction, which is called dapsone hypersensitivity syndrome (DHS), is associated with an allele in the human leukocyte antigen, HLA-B*13:01. In the light of validating the association of HLA-B*13:01 with DHS in a leprosy endemic area like Indonesia, we conducted a study involving leprosy patients who had DHS during the course of their multi-drug treatment as well as leprosy patients who managed to complete their course of treatment without exhibiting DHS. The results of this study validated the association of HLA-B*13:01 and DHS at a very significant level of evidence and the odds of people carrying at least one allele is 233.3-times the risk of non-carriers. This allele was also able to predict a person at risk of DHS 95% of the time. Thus, screening of HLA-B*13:01 to prevent DHS is warranted. [ABSTRACT FROM AUTHOR]

• Phase III study was conducted in moderate-to-severity plaque psoriasis patients. • SCT630 and adalimumab showed equivalences in efficacy and similar safety. • Switching from adalimumab to SCT630 did not impact safety or efficacy. This phase III study aimed to compare the efficacy, safety, and immunogenicity of SCT630 with the reference adalimumab. A total of 367 Chinese patients with moderate-to-severe plaque psoriasis were randomly assigned to receive 80 mg of SCT630 or adalimumab subcutaneously at week 1, 40 mg at week 2, then 40 mg biweekly. At week 16, those with 50 % or more improvement in psoriasis area and severity index (PASI) were eligible to enter an extension period up to week 52. Patients on SCT630 continued the same treatment, whereas patients receiving adalimumab were re-randomized at a ratio of 1:1 to adalimumab or SCT630 group. The primary endpoint was percentage improvement in PASI at week 16. Other endpoints included PASI 50/75/90/100, Physician's Global Assessment, Dermatology Life Quality Index, safety, and immunogenicity. PASI improvement at week 16 was 85.07 % for SCT630 and 84.82 % for adalimumab. The mean difference (3.10 %, 95 % CI: −1.875 %, 8.066 %) was within the equivalence interval. Other efficacy endpoints, safety and immunogenicity profiles were similar across the two groups. There were no safety or immunogenicity difference between switched/continued groups. This phase III study demonstrated the equivalences in efficacy, safety and immunogenicity of SCT630 to adalimumab in patients with moderate to severe psoriasis. [ABSTRACT FROM AUTHOR]

Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmented anomaly mainly affecting flexures. Though KRT5 has been identified to be the causal gene of DDD, the heterogeneity of this disease was displayed: for example, POFUT1 and POGLUT1 were recently identified and confirmed to be additional pathogenic genes of DDD. To identify other DDD causative genes, we performed genome-wide linkage and exome sequencing analyses in a multiplex Chinese DDD family, in which the KRT5 mutation was absent. Only a novel 1-bp deletion (c.246+5delG) in POFUT1 was found. No other novel mutation or this deletion was detected in POFUT1 in a second DDD family and a sporadic DDD case by Sanger Sequencing. The result shows the genetic-heterogeneity and complexity of DDD and will contribute to the further understanding of DDD genotype/phenotype correlations and to the pathogenesis of this disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate the histological classification of melasma with reflectance confocal microscopy (RCM) in vivo. Methods: Two hundred and ten cases with facial melasma lesions were enrolled. After informed consent, the target melasma lesion of 10 patients were imaged with RCM and then biopsied as well. Under the RCM scanning, the distribution of the melanin determined the histological types, and then, the results of RCM images were compared with those of the histopathology. The other 200 cases were tested only with RCM. Results: For the 10 cases imaged and biopsied, compared with that of the perilesional normal skin, the amount of melanin was significantly increased in the epidermis in all lesions under RCM, while three cases also found melanin in the dermis. Thus, seven of the10 patients were categorized as the epidermal type while the other three as mixed ones, and the results were well correlated with those of the histopathology. Of the other 200 patients, 143 cases 71.5%) were categorized as the epidermal type while the other 57 (28.5%) cases as mixed ones. Limitations: If more melasma cases are biopsied, the data will be more convincing. Conclusion: RCM in vivo analysis shows complete coherence with histopathology results, which could be an alternative for the classification of melasma, and based on the results of RCM imaging, melasma is classified into two major types: the epidermal type and mixed type. [ABSTRACT FROM AUTHOR]

The article focuses on the Genome-Wide Association Study of single nucleotide polymorphisms (SNP) of association of PARK2 and PACRG with leprosy in Chinese population. The study found no remarkable association of Chinese population with the risk SNPs within the PARK2 and PACRG leprosy region. It is noted that there may be a suggestive association of SNPs with ethnic heterogeneity of susceptibility to leprosy.

Porokeratosis (PK) is a group of epidermal keratinization disorder exhibiting an autosomal dominant mode of inheritance, including five clinical subtypes: disseminated superficial actinic porokeratosis (DSAP), disseminated superficial porokeratosis (DSP), classic porokeratosis of Mibille (PM), porokeratosis palmaris et plantaris disseminate (PPPD) and linear porokeratosis (LP).To date, seven genes, MVK, MVD, FDPS, PMVK, SSH1, SART3 and SLC17A9 in six genetic loci, have been reported to be involved in the PK development, accounting for about 70% of patients [[1]]. Besides, three of the LP patients carried one PMVK mutation and two MVD mutations respectively, which is consistent with previous reports [[2], [5]]. [Extracted from the article]

Background Generalized pustular psoriasis (GPP) is a rare type of psoriasis with potentially life-threatening implications. Mutations in IL36RN gene have been suggested to be causative or predisposing factors for GPP. Objective To evaluate the genetic heterogeneity of GPP, PV and GPP alone, GPP with PV. Methods We performed a sanger sequencing identify IL36RN mutations in 62 Chinese Han patients with sporadic GPP, including 17 GPP without psoriasis vulgaris (PV) (GPP alone) cases vs. 45 GPP with preceding, later or accompanied by PV (GPP with PV) cases; 16 patients with pediatric-onset GPP (PGPP) vs. 46 adult-onset GPP (AGPP). We included 96 healthy controls and 174 sporadic patients with PV. Resuts We found 2 new variants and 4 known IL36RN variants in 29 GPP patients, 18 individuals carried recessive (homozygous/compound heterozygous) alleles and 11 cases harbored a single heterozygous change. Twelve PV patients and six controls harbored a single heterozygous for three out of the six variants. Significant differences were observed between GPP and PV groups, GPP alone and GPP with PV groups when compared frequencies of IL36RN variants, but we did not found association between PGPP and AGPP groups. Conclusion Our study provided more evidence that GPP and PV are distinct subtypes of psoriasis caused by different pathogenesis, and GPP alone could be regarded as an especial entities of GPP which is different from GPP with PV on the etiology. [ABSTRACT FROM AUTHOR]

Summary Objective Leprosy and tuberculosis (TB) are chronic granulomatous infectious diseases. As well as pathogen and environmental factors, host genetic factors make a substantial contribution to susceptibility to both diseases. More importantly, leprosy and TB also have pathogenic mechanisms and clinical features in common. In this study, the genetic association between leprosy and TB was investigated in a Chinese Han population. Methods A genetic association study that included 46 TB susceptibility single nucleotide polymorphisms (SNPs) was performed, involving 1150 leprosy cases and 1150 controls from the Chinese Han population. The Sequenom MassARRAY system was used. Results No significant association was found between the 46 SNPs and leprosy. Therefore, according to the present study, there is no shared susceptibility locus between leprosy and TB in the Chinese Han population. Conclusions Although leprosy and TB have a number of similar characteristics, no shared susceptibility loci were found in the Chinese Han population. Thus, this study demonstrated that the genetic basis of the pathogenesis of the two diseases may vary greatly. [ABSTRACT FROM AUTHOR]