Serine protease inhibitor B7 (SERPINB7) mutations have been reported to cause Nagashima-type palmoplantar keratosis (NPPK), but their biological effects are largely unknown. We conducted whole-exome sequencing and identified a c.796C>T (p.Arg266Ter) mutation in SERPINB7 in a Chinese pedigree, which presented as an autosomal recessive inheritance pattern. We assessed the function of SERPINB7 in homozygous and heterozygous mutation carriers, and the results suggested that the single c.796C>T mutation may alter the subcellular localization of SERPINB7. One of the homozygous mutation patients (II-3) was treated with ixekizumab and showed moderate improvement in keratinization. In addition, we analysed the spatiotemporal expression of serpinb1l1 and serpinb1l3, the zebrafish homologue of human SERPINB7, which is expressed in larvae and adults. In larvae, both serpinb1l1 and serpinb1l3 were expressed in the digestive tract. Then, we performed RT-PCR on adult fins based on similarity to the site of NPPK expression in humans and found that the genes were expressed in five fins (pectoral, pelvic, dorsal, anal and caudal) of the zebrafish distal extremity. Taken together, our results demonstrated that the single c.796C>T (p.Arg266Ter) mutation may alter the location of SERPINB7-encoded protein in the skin, while zebrafish SERPINB7 homologue was expressed in adult fins. These findings will enable us to construct knock-out models to explore the pathogenesis of palmoplantar keratosis.

UNASSIGNED: Hyperkeratosis of the nipple and areola (HNA) is a rare skin disease with unknown etiology. Some patients are misdiagnosed or never diagnosed, especially during the early stage of this disease. In addition, the mechanism involved in the development of HNA is still unknown, and genomic alterations have not been reported anywhere.
UNASSIGNED: A 26-year-old female suffered gradual bilateral areola thickening and enlargement, with accompanying intense itching, and was diagnosed with HNA at the First Affiliated Hospital of Chongqing Medical University. No obvious abnormalities were found in laboratory test examinations such as hormone testing for estrogen, progesterone, or prolactin. Typical papillomatous skin with orthokeratotic hyperkeratosis and numerous infiltrating lymphocytes was detected through a histopathological examination. The results from RNA-sequencing showed that the molecular expression between HNA and a normal nipple and areola (NNA) was obviously different. No significant difference was found in the bilateral lesions. In addition, immune-related cell signaling pathways were overactivated in HNA compared to the control HNA.
UNASSIGNED: The typical symptoms, clinical features, and histopathological alterations presented in this case lead to a profound understanding of HNA, which can avoid the misdiagnosis and missed diagnosis of this disease at an early stage. The dysfunction of the local immune system, which was demonstrated by pathological examination and genomic analysis, suggests that anti-autoimmune therapy, such as steroid medication, may be an effective treatment for HNA at an early stage.

UNASSIGNED: The available treatments for refractory hyperkeratotic eczema are inadequate with frustrating results. We, therefore, incorporated Calcipotriol and Betamethasone Dipropionate (Daivobet®), and Viaminate into the mainstay treatment to improve the clinical symptoms. The study aimed to evaluate the efficacy of Daivobet ® and Viaminate as a potential treatment alternative for refractory hyperkeratotic eczema.
UNASSIGNED: Between 2013 and 2015, 61 patients diagnosed with refractory hyperkeratotic eczema (RHE) who had shown inadequate response to conventional therapies were pooled from a single center. Besides, they were all treated with Daivobet ® , Viaminate, and an occlusive dressing mixture containing 5% salicylic acid ointment and 25% zinc oxide paste following inadequate response to conventional therapies (corticosteroids plus 25% zinc oxide paste and 5% salicylic acid ointment). Investigators Global Assessment (IGA) and Patient-Oriented Eczema Measure (POEM) assessed baseline and outcome measures for the degree of hyperkeratinization (0-clear; 3-moderate; 4-severe).
UNASSIGNED: Of the 61 patients, 49 (80.3%) patients presented with moderate RHE and 12 (19.7%) with severe RHE. After 24 weeks of treatment, the period for loss of keratinization was significantly lower in patients with moderate RHE (3.9±1.9 weeks) than those with severe RHE (10.8±1.0 weeks) with a P-value <0.01. Furthermore, they required a significantly shorter total treatment duration (10.6 ± 4.3 weeks) than those with severe RHE (20.3±3.6 weeks) with a P-value of <0.01. However, there were no significant differences in post hoc analysis at week 36 with P-values of 0.46 and 1.00 for IGA and POEM, respectively.
UNASSIGNED: Our results showed that the incorporation of Viaminate and Daivobet® into mainstay treatment was effective and safe for the long-term management of RHE.

Foot hyperkeratosis is common. They often coincide with fungal infections, are difficult to cure and relapse rates are high. In this case study, longstanding and intractable plantar hyperkeratotic lesions were investigated for potential causative agents by histological examinations, by using human cell culture medium to grow the infected skin tissue, by sequencing ribosomal DNA and whole genome. Aspergillus sydowii was identified as the pathogen in the hyperkeratotic lesions. A peculiars intracellular infection of the fungus appeared to merge with anucleated epithelial cells of the skin, in which not fungal cells but basophilic nucleus-like bodies and abundant fungal proteins were seen in the cells. The composite fungal-human zombie-like cells were found to grow in the culture and in hyperkeratotic lesions, and some were readily transformed to natural fungus. Such zombie cells might play roles in the pathogenesis and recurrences of plantar hyperkeratotic lesions, resistance to antifungal drugs and relapses of the fungal infections.

Zhao C, Li Y, Shi G, Shi X, Zhang G. A novel Y160C mutation of Keratin 10 gene in a Chinese male infant with epidermolytic hyperkeratosis. Turk J Pediatr 2018; 60: 426-428. Epidermolytic hyperkeratosis (EHK) is a rare genodermatosis whose prevalence is less than 1 in 100,000. Mutations in either the keratin 1 or keratin 10 genes lead to EHK characterized by congenital erythema and epidermal blisters at birth, followed by hyperkeratotic skin lesions with age. We here report a 1-and-a-half-year-old male infant with EHK caused by a novel mutation, c.479A > G, g.489A > G, p. Y160C, of the keratin 10 gene. Mutation at this position has been reported previously, but the type of amino acid change was different. These results expand the database of keratin 10 gene mutations.

Oral leukoplakia (OLK) is one of the most common oral potentially-malignant disorders (OPMD) with complex causes, a long disease course and a high tendency for recrudescence. Although a variety of methods exist for treating this disease, canceration rates remain high. Herein, we described a case of 72-year-old male patient with OLK of the palatine mucous membrane who had achieved complete remission after being treated with five sessions of plum-blossom needle (PBN) assisted 5-aminolevulinic acid-photodynamic therapy (ALA-PDT). The patient had since been subsequently placed under close observation (>12 mo). To date, there has been no recurrence. PBN assisted PDT might be suitable for the treatment of OPMDs in patients presenting with epithelial hyperkeratosis.

BACKGROUND: Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before.
METHODS: Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later.
CONCLUSIONS: We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.

Residents of the Bayingnormen region of Inner Mongolia have been exposed to arsenic-contaminated well water for over 20 years, but relatively few studies have investigated health effects in this region. We surveyed one village to document exposure to arsenic and assess the prevalence of arsenic-associated skin lesions and self-reported morbidity. Five-percent (632) of the 12,334 residents surveyed had skin lesions characteristics of arsenic exposure. Skin lesions were strongly associated with well water arsenic and there was an elevated prevalence among residents with water arsenic exposures as low as 5 microg/L-10 microg/L. The presence of skin lesions was also associated with self-reported cardiovascular disease.