Dietary habits in adult Japanese patients with vitiligo.

Vitiligo is an autoimmune skin disease with acquired depigmentation. Dietary habits may modulate the pathogenesis of vitiligo. We evaluated dietary habits in adult Japanese patients with nonsegmental vitiligo, and compared their results with those of age- and sex-matched controls. We also examined the relationship between dietary habits and Vitiligo Area Scoring Index (VASI), or vitiligo on different anatomical sites. The intakes of energy, nutrients, and foods in the participants were analyzed using a brief-type self-administered diet history questionnaire. Patients with vitiligo showed higher body mass index (BMI) and lower intakes of manganese, vitamin D, pulses, and confection, compared with controls. Multivariate logistic regression analysis showed that vitiligo was associated with high BMI. VASI was higher in males than in females, and negatively correlated with age or intakes of potatoes and vegetables other than green/yellow vegetables. Linear multivariate regression analysis showed that high VASI was associated with younger age. Multivariate logistic regression analysis showed that moderate to severe vitiligo (VASI ≥ 4.25) was associated with male sex and longer disease duration. Multivariate logistic regression analyses showed the following association with vitiligo on respective anatomical sites: high intake of eggs and dairy products and high VASI on the head or neck, high intake of oils and fats and high VASI on the trunk, high intake of cereals and high VASI on the upper limbs, male sex and high VASI on the lower limbs, and high BMI and high VASI on the hands or feet. In conclusion, the control of obesity might have prophylactic or therapeutic effects on vitiligo.

Laser capture microdissection provides a novel molecular profile of human primary cutaneous melanoma.

Melanoma accounts for the majority of skin cancer-related mortality, highlighting the need to better understand melanoma initiation and progression. In-depth molecular analysis of neoplastic melanocytes in whole tissue biopsies may be diluted by inflammatory infiltration, which may obscure gene signatures specific to neoplastic cells. Thus, a method is needed to precisely uncover molecular changes specific to tumor cells from a limited sample of primary melanomas. Here, we performed laser capture microdissection (LCM) and gene expression profiling of patient-derived frozen sections of pigmented lesions and primary cutaneous melanoma. Compared to bulk tissue analysis, analysis of LCM-derived samples identified 9528 additional differentially expressed genes (DEGs) including melanocyte-specific genes like PMEL and TYR, with enriched of pathways related to cell proliferation. LCM methodology also identified potentially targetable kinases specific to melanoma cells that were not detected by bulk tissue analysis. Taken together, our data demonstrate that there are marked differences in gene expression profiles depending on the method of sample isolation. We found that LCM captured higher expression of melanoma-related genes while whole tissue biopsy identified a wider range of inflammatory markers. Taken together, our data demonstrate that LCM is a valid approach to identify melanoma-specific changes using a relatively small amount of primary patient-derived melanoma sample.

Prenatal Torsion of Radial Polydactyly: A Gangrenous Mass at the Base of the Thumb.

A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important.

Novel TRPS1 frameshift variant in tricho-rhino-phalangeal syndrome type I accompanied by zinc deficiency.

Tricho-rhino-phalangeal syndrome type I (TRPS1), caused by pathogenic variants in the transcriptional repressor GATA-binding 1 gene (TRPS1), is characterized by ectodermal and skeletal anomalies including short stature and sparse scalp hair during infancy. TRPS1 encodes a zinc finger protein transcription factor that contributes to bone homeostasis by regulating perichondral mineralization, chondrocyte proliferation, and apoptosis. Here, a male infant aged 14 months presented with sparse scalp hair, deformed nails, fused teeth, and postnatal growth retardation without neurodevelopmental disorder. As endocrinological measurements revealed low serum zinc levels, he was treated with zinc acetate hydrate, which improved his growth velocity and scalp hair. Whole-exome sequencing revealed that this patient harbored a novel pathogenic de novo heterozygous TRPS1 frameshift variant, c.2819_2822del, p.(His940Argfs*6). Zinc deficiency induces zinc finger protein dysfunction via effects on protein folding and assembly, affecting target gene transcription and apoptosis. The symptoms of TRPS1 are similar to those caused by inadequate levels of zinc, an essential trace element with important roles in tissue growth and repair. Accompanying zinc deficiency may have affected the function of important zinc finger proteins, resulting in phenotypic deterioration. Analysis of zinc metabolism in patients harboring TRPS1 variants will enhance understanding the variety of phenotypes of TRPS1.

Dietary habits in Japanese patients with bullous pemphigoid: low intake of retinol.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Dietary habits may modulate the pathogenesis of BP. OBJECTIVES: We evaluated dietary habits in Japanese patients with BP and compared their results to those of age- and sex-matched healthy controls. We also examined the relationship between dietary habits versus IgG anti-BP180NC16A antibody or parameters of BP disease area index (BPDAI); cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. MATERIALS & METHODS: Dietary habits were assessed by the validated, Brief-type self-administered Diet History Questionnaire. Severity of disease was assessed with BPDAI. RESULTS: Patients with BP showed a lower intake of retinol (vitamin A1) and beverages, and a higher intake of seasoning/spices, compared to controls. The bivariate and multivariable logistic regression analysis showed that BP was associated with a low intake of retinol and beverages. There were no significant correlations between IgG anti-BP180NC16A antibody levels and intake of nutrients/foods. The BPDAI score for cutaneous blisters/erosions significantly positively correlated with intake of carbohydrate and negatively with intake of retinol, vitamin A, animal fat, cholesterol, phosphorus, and vitamin B2. The BPDAI score for cutaneous urticaria/erythema significantly negatively correlated with intake of vitamin A. BP patients with mucosal blisters/erosions had a higher intake of cholesterol, n-6 polyunsaturated fatty acid, and eggs, and lower intake of seasoning/spices, compared to patients without BP. CONCLUSION: The supplementation of vitamin A might have prophylactic and/or therapeutic effects on BP.

Machine learning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals.

BACKGROUND AND AIMS: Accurate risk stratification for hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) is necessary for optimal surveillance. We aimed to develop and validate a machine learning (ML) model to predict the risk of HCC after achieving an SVR in individual patients. METHODS: In this multicenter cohort study, 1742 patients with chronic hepatitis C who achieved an SVR were enrolled. Five ML models were developed including DeepSurv, gradient boosting survival analysis, random survival forest (RSF), survival support vector machine, and a conventional Cox proportional hazard model. Model performance was evaluated using Harrel' c-index and was externally validated in an independent cohort (977 patients). RESULTS: During the mean observation period of 5.4 years, 122 patients developed HCC (83 in the derivation cohort and 39 in the external validation cohort). The RSF model showed the best discrimination ability using seven parameters at the achievement of an SVR with a c-index of 0.839 in the external validation cohort and a high discriminative ability when the patients were categorized into three risk groups (P <0.001). Furthermore, this RSF model enabled the generation of an individualized predictive curve for HCC occurrence for each patient with an app available online. CONCLUSIONS: We developed and externally validated an RSF model with good predictive performance for the risk of HCC after an SVR. The application of this novel model is available on the website. This model could provide the data to consider an effective surveillance method. Further studies are needed to make recommendations for surveillance policies tailored to the medical situation in each country. IMPACT AND IMPLICATIONS: A novel prediction model for HCC occurrence in patients after hepatitis C virus eradication was developed using machine learning algorithms. This model, using seven commonly measured parameters, has been shown to have a good predictive ability for HCC development and could provide a personalized surveillance system.

Pancreaticoduodenal Artery Aneurysm Rupture Presenting as Duodenal Obstruction Successfully Treated with Early Transcatheter Arterial Embolization: A Case Report of Suspected Segmental Arterial Mediolysis.

Visceral aneurysms are a rare but important form of abdominal vascular disease. Rupture of the aneurysms leads to serious symptoms, such as acute abdomen or abdominal bleeding. However, duodenal obstruction due to arterial rupture of an aneurysm is very rare. We herein report a 50-year-old woman with suspected segmental arterial mediolysis (SAM) who was first diagnosed with acute abdomen and duodenal obstruction. Rupture of a pancreaticoduodenal artery aneurysm was confirmed, and she was treated with transcatheter arterial embolization. In cases of acute abdomen, SAM is a rare but important possibility to consider as a differential diagnosis.

Case of bullous pemphigoid refractory to corticosteroids by antiepileptic drug-induced CYP3A4.

The most common treatment option for patients with bullous pemphigoid is systemic corticosteroids. CYP3A4, a drug-metabolizing enzyme in the liver, metabolizes synthetic steroids to a varying degree. Although there are many CYP3A4-inducing drugs, several antiepileptic drugs, such as phenytoin and phenobarbital, strongly induce CYP3A4, thereby reducing the effects of corticosteroids. Here, we report a case of refractory bullous pemphigoid that rapidly improved after the discontinuation of phenytoin and phenobarbital. To achieve adequate pharmacological effects of corticosteroids, we must always ensure that patients who require corticosteroids for treatment are not medicated with CYP3A4-inducing agents.

Development of pemphigus vegetans and exacerbation of pemphigus foliaceus after secukinumab loading in a patient with complicated generalized pustular psoriasis and pyoderma gangrenosum.

In dermatology, biologics that block signaling pathways of TNF-α, IL-4/IL13, IL-17s, and IL-23 are widely used for the treatment of several inflammatory skin diseases, such as atopic dermatitis and psoriasis. They have shown excellent efficacy with an acceptable safety profile. However, these biologics targeting pathogenic cytokines and their receptors could modulate immunological balance, leading to the development of other inflammatory or autoimmune skin diseases in some cases. In this study, we present a patient who suffered pemphigus vegetans and showed an exacerbation of pemphigus foliaceus after secukinumab loading for the treatment of complicated generalized pustular psoriasis and pyoderma gangrenosum.

Spontaneous regression of a rectal tonsil presenting as a large submucosal tumor.

Rectal tonsils are localized hyperplastic lymphoid tissues in the rectum, and the initial endoscopic findings are consistent with those for neoplastic lesions. However, rectal tonsils are benign entities, and the diagnosis should be made cautiously. A 70-year-old man presented with pain on defecation with rectal bleeding. Colonoscopy revealed a 3-cm protruding mass in the rectum with mucosal erosion, but no malignant features were observed on forceps biopsy. Endoscopic ultrasonography (EUS) showed that the lesion was a hypoechoic mass without blood flow. Fine needle aspiration under EUS revealed no malignant components, although the size of the lesion had shrunk, and symptoms, such as blood-stained stool, tenesmus, and discomfort during defecation, had resolved. A second forceps biopsy showed intermediate-sized lymphocytes without lymphoepithelial lesions. Based on immunostaining, the lesion was diagnosed as a rectal tonsil. Rectal tonsils occur due to localized proliferation of reactive lymphoid follicles in the submucosa or muscularis mucosa. However, endoscopic diagnosis is difficult since less invasive treatment is performed for neoplastic lesions of the rectum to preserve the function of the anal sphincter. Diagnosis and treatment of small lesions might be possible by endoscopic resection; however, for relatively large lesions, formulating a diagnosis based only on biopsy specimens becomes even more difficult. Therefore, repeated biopsies might be helpful for the diagnosis of rectal tonsils and for excluding other neoplasms.