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Recent studies indicate that hepatic diseases are associated with psoriasis. Non-invasive tests, including the Fibrosis-4 (FIB-4) index, which can confidently rule out the presence of advanced fibrosis, are currently receiving attention. However, data on the FIB-4 index in psoriasis patients and the effects of biologics on the FIB-4 index are limited. We investigated the relationships between the FIB-4 index and demographic or clinical characteristics as well as the effects of biologics on the FIB-4 index in psoriasis patients. Psoriasis patients aged 36-64 years, whose treatment was initiated with interleukin (IL)-17 inhibitors or IL-23 inhibitors for psoriasis from May 2015 to December 2022, were consecutively included. Data were collected retrospectively from the patients' charts. A total of 171 psoriasis patients were included in this study. Thirty-four, 43, 21, 32, and 41 psoriasis patients were treated with secukinumab, ixekizumab, brodalumab, guselkumab, or risankizumab, respectively. In biologics-naïve patients, a significant but weak positive correlation was observed between the FIB-4 index and age (r = 0.3246, p = 0.0018). There was no significant correlation between the FIB-4 index and other demographic or clinical characteristics. Regarding the effects of biologics on the FIB-4 index, no significant change was observed in psoriasis patients treated with any biologics. However, in psoriasis patients with a baseline FIB-4 index of >1.3, patients treated with guselkumab and those treated with either IL-23 inhibitor showed significantly decreased FIB-4 index scores 6 months after initiating the biologics (p = 0.0323, p = 0.0212). In contrast, no change was observed in FIB-4 index scores in patients treated with IL-17 inhibitors. In conclusion, our study revealed that the FIB-4 index was correlated with age in psoriasis patients. Furthermore, IL-23 inhibitors (but not IL-17 inhibitors) decreased the FIB-4 index score at 6 months in psoriasis patients with elevated FIB-4 index scores at baseline. Further studies are needed to clarify whether IL-23 inhibitors improve liver fibrosis physiologically and functionally., (© 2024 Japanese Dermatological Association.)

Renpenning syndrome (OMIM: 309500) is a rare X-linked disorder that causes intellectual disability, microcephaly, short stature, a variety of eye anomalies, and characteristic craniofacial features. This condition results from pathogenic variation of PQBP1, a polyglutamine-binding protein involved in transcription and pre-mRNA splicing. Renpenning syndrome has only been reported in affected males. Carrier females do not usually have clinical features, and in reported families with Renpenning syndrome, most female carriers exhibit favorable skewing of X-chromosome inactivation. We describe a female with syndromic features typical of Renpenning syndrome. She was identified by exome sequencing to have a de novo heterozygous c.459_462delAGAG mutation in PQBP1 (Xp11.23), affecting the AG hexamer in exon 4, which is the most common causative mutation in this syndrome. Streaky hypopigmentation of the skin was observed, supporting a hypothesized presence of an actively expressed, PQBP1 mutation-bearing X-chromosome in some cells. X-inactivation studies on peripheral blood cells demonstrated complete skewing in both the proband and her mother with preferential inactivation of the maternal X chromosome in the child. We demonstrated expression of the PQBP1 mutant transcript in leukocytes of the affected girl. Therefore, it is highly likely that the PQBP1 mutation arose from the paternal X chromosome., (© 2019 Wiley Periodicals, Inc.)

The association of psoriasis with thyroid dysfunction has been investigated; however, it remains controversial. Some papers indicate it, and others do not. Thereby, we investigated the prevalence of thyroid dysfunction in patients with psoriasis vulgaris (PsV), psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP), and the relationship between the severity of psoriasis with serum free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone levels. Data on 85 psoriatic patients visiting our hospital from January 2015 to November 2017 (54 men and 31 women; 51 PsV, 23 PsA 23 and 11 GPP) were retrospectively analyzed. Fourteen percent of psoriatic patients had thyroid dysfunction. The percentage of patients with thyroid dysfunction was the highest in those with GPP (45% GPP, 13% PsA, 8% PsV). Patients with thyroid dysfunction demonstrated significantly higher Psoriasis Area and Severity Index scores and elevated serum C-reactive protein (CRP) levels than those without thyroid dysfunction. A significant negative correlation was observed between the serum levels of CRP and fT3 (P = 0.0032, r = -0.4635). Our data indicate that thyroid dysfunction in patients with psoriasis is associated with inflammation caused by psoriasis., (© 2019 Japanese Dermatological Association.)

Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that presents with erythema and sterile pustules, pathologically characterized by Kogoj's spongiform pustules. GPP is sometimes accompanied by mucosal involvement, and the most common lesion is on the tongue. IL36RN mutation was found to contribute to the pathogenesis of GPP especially in patients who develop GPP without a past medical history of psoriasis vulgaris. The association of IL36RN mutation with mucosal involvement in GPP is controversial. We herein report a 60-year-old male GPP patient with no past history of plaque psoriasis presenting with not only severe skin lesions and arthritis but also severe mucosal involvements of pharyngeal and gastrointestinal lesions, which led to gastrointestinal bleeding. Our case did not have any mutation in the IL36RN gene. We should be aware that severe GPP can cause gastrointestinal bleeding. The relevancy of IL36RN mutation with mucosal involvement in GPP remains to be elucidated., (© 2018 Japanese Dermatological Association.)

Bullous pemphigoid (BP) is an acquired autoimmune blistering disease in which autoantibodies against epitopes in the basement membrane zone of the skin such as BP180 or BP230 are produced. Dipeptidyl peptidase (DPP)-4 inhibitors have become commonly used to treat diabetes. As DPP-4 inhibitors are more commonly prescribed for diabetes, BP related to DPP-4 inhibitors has been reported and has attracted attention. Therefore, we retrospectively investigated patients who were diagnosed with BP in order to examine characteristics of DPP-4 inhibitor-related BP (nine patients; median age, 85 years) in comparison with non-DPP-4 inhibitor-related BP (21; median age, 85 years). There was no significant difference in Bullous Pemphigoid Disease Area Index between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients, except for erosions/blisters score in mucosa. Laboratory tests revealed no significant differences between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients in total white blood cell count, eosinophil count, neutrophil count and the titer of anti-BP180 antibody. The number of eosinophils infiltrating into the skin was significantly lower in patients with DPP4 inhibitor-related BP than in patients with non-DPP4 inhibitor-related BP. Our results showed that DPP-4 inhibitor-related BP has some distinct pathological characteristics from BP not associated with DPP-4 inhibitor., (© 2018 Japanese Dermatological Association.)

Pseudohypoparathyrodism (PHP) is a disorder caused by mutations in the guanine nucleotide-binding α-subunit (GNAS). We sought to determine the genetic origin of PHP1a in one affected family. We identified the previously reported Gsα R231H mutation in family members affected with PHP1a. DNA analysis found that the two clinically affected sons are heterozygous for the mutation. The sons have PHP1a, manifesting obesity, intellectual disability, hypogonadism, hypothyroidism and elevated PTH levels. Initial DNA sequencing did not detect the mutation in either parent. However, their mother displayed some features of PHP, including elevated PTH levels and asymmetrical metacarpal shortening. Using molecular cloning, we detected the mutation at low levels in the mother's leukocyte DNA, consistent with somatic mosaicism and her mildly affected status. Thus, we have identified additional cases of PHP1a caused by the Gsα R231H mutation. In this family, the mother has a milder phenotype due in part to somatic mosaicism, whereas the two affected sons have full PHP1a. Though somatic mosaicism for activating GNAS mutations is known to occur in McCune-Albright syndrome, this is the first report confirming somatic mosaicism for a hypofunctioning GNAS mutation in a PHP kindred., (© 2010 Wiley-Liss, Inc.)

We report on a 14-year-old boy who presented with bilateral cleft lip and palate, hearing loss, a language processing disorder, and mild mental retardation (MR). G-banded chromosome analysis of the patient and his family revealed he carried an apparently balanced de novo complex translocation involving chromosomes 5, 6, and 7. Chromosomal comparative genomic hybridization (CGH) was performed to investigate the possibility of any genomic imbalance as a result of the complex rearrangement. No abnormality was detected at any of the translocation breakpoint regions (5p13.2, 6p24, 7q21.1, and 7q21.3), nor was there any other imbalance which fell inside our significance level of 0.8-1.2. Array-CGH analysis was initiated to perform a higher resolution search for gains and losses, and revealed a deletion of two adjacent clones, CTB-133K23 and RP11-112P4, mapping to 7q31.3, which are 4.4 Mb apart. Fluorescence in situ hybridization (FISH) using these two clones confirmed the deletion. 7q31 has frequently been implicated in the search for genes involved in speech and language disorders. The specific 7q31.3 region deleted in our patient has significant overlap with some such areas of the genome. These findings are, therefore, of value in identifying genes involved in the speech and language phenotypes. This study has shown the importance of array-CGH in investigating patients who have clinical features suggestive of a chromosome abnormality, but with apparently balanced chromosome rearrangements. It has demonstrated that the array-CGH technique provides a much greater insight into submicroscopic chromosome imbalances than conventional cytogenetic techniques.