Tomohisa Fukui

Trichoscopic Findings of Erosive Pustular Dermatosis of the Scalp Associated with Gefitinib

Alopecia associated with epidermal growth factor receptor (EGFR) inhibitor therapy is a rare cutaneous side effect with the potential to progress to scarring alopecia. Thus, dermatologists should make an early diagnosis. We present the case of a 57-year-old Japanese female with scarring alopecia associated with gefitinib, which is an EGFR inhibitor, including trichoscopic findings. The patient treated with gefitinib for non-small cell lung cancer experienced skin rash and hair loss of the scalp. The scalp lesions appeared similar to erosive pustular dermatosis of the scalp. Trichoscopic examination showed follicular keratotic plugging, milky red areas, white patches, hair shaft disorder, tapering hair, and absence of follicular opening. Histological examination showed ruptured hair follicles with a perifollicular infiltration of plasma cells, lymphocytes, and histiocytes. Oral minocycline and topical steroid treatment produced no improvement. With a reduction in the gefitinib dosage, alopecia gradually improved, although scarring remained. We consider these trichoscopic findings and suspect that follicular keratotic plugging might be a finding associated with scarring alopecia due to EGFR inhibitor therapy.

Mycosis fungoides bullosa associated with bullous pemphigoid

recent primary infection, whereas the presence of a highavidity antibody indicates a past or recurrent infection. Moreover, during active infections, HHV-6 and HHV7 may cross-react. An IgM response to HHV-7 primary infection, therefore, may also be directed to HHV-6 with a reciprocal rising in antibody titer to both viruses. In neonates, maternal IgGs, which may persist to up to six months of age, interfere with the diagnosis of both HHV-6 and HHV-7 infections. Therefore, in the presence of symptoms compatible with primary HHV-6 infection during the first months, such as seizures accompanied by a cutaneous rash, the diagnosis may need, in addition to the detection of specific IgM, quantitative PCR testing. After primary infection, HHV-6 and HHV-7 remain latent in the body mostly in the salivary glands. Serologic assays cannot be sufficient to diagnose viral reactivations, and direct methods like PCR are preferred. Among the latter, however, the detection of the viral genome is not synonymous of active infection and only bona fide quantitative methods, which measure the HHV-6 and HHV-7 viral load in tissues, blood cells and, particularly, plasma and serum, are diagnostic, also permitting the follow-up of the active infection and suggesting a causal link. In addition, in diseases such as pityriasis rosea, which are most probably associated with the active replication of either or both HHV-6 and HHV-7, quantitative PCR assays may detect only one virus depending on the particular phase of the disease. In pityriasis rosea, HHV-7 behavior is unique. It replicates before HHV-6, but its replication tends to cease in the advanced phases. Another issue that involves quantitative methods is the possibility of chromosomal integration (ci) of HHV-6 that complicates the interpretation of a high viral load. In fact, subjects carrying ciHHV-6 present with high levels of HHV DNA in plasma, which, however, persist over time. In these cases, comparisons of the effects of viral loads on multiple fluids and tissues, together with methods that detect the expression of HHV-6 genes associated with a productive infection and measures of lytic antigens in blood cells, may help to distinguish an active infection from a ciHHV-6 state. Lastly, immunohistochemistry can detect viral antigens expressed only during a given moment in the virus replication cycle, thereby indicating the status of the infection.

Anti-laminin γ1 pemphigoid associated with ulcerative colitis and psoriasis vulgaris showing autoantibodies to laminin γ1, type XVII collagen and laminin-332.

Anti-laminin γ1 pemphigoid is a novel autoimmune subepidermal bullous disease characterized by the presence of circulating immunoglobulin (Ig) G autoantibodies to laminin γ1, a common constituent at various basement membrane zones (BMZs). Although an association between various subepidermal blistering diseases and inflammatory bowel disease (IBD) has been reported, there have been no previous reports on an association between anti-laminin γ1 pemphigoid and IBD. Here, we demonstrate a case of anti-laminin [...]

Immunosuppressive effect of adipose-derived stromal cells on imiquimod-induced psoriasis in mice

In the present study, we investigated a potential influence of the HLA-DQB1 promoter polymorphisms on the development of NSV in the Korean population. One HLA-DQB1 SNP (rs9274552) demonstrated an association with NSV. In the haplotype analysis, the C-G and A-G haplotypes were significantly associated with NSV. To find whether these promoter SNPs affect transcription factors, the online program AliBaba 2.1 (http://www.gene-regulation.com/pub/programs/alibaba2) was used. At the rs9274552 SNP, the A-containing sequences bind with C/EBPa1p transcription factor, but C/EBPa1p disappears in the C-containing sequences. At the rs9274579 SNP site, the A-containing sequences interact with Oct-1, but Oct-1 transcription factor disappear in the G-containing sequences. Assuming the change of transcription factors according to variants of SNPs, these promoter SNPs may influence gene and protein expression of HLA-DQB1. Our results indicate that the HLA-DQB1 promoter polymorphism (rs9274552) may increase susceptibility to NSV in Korean population along with genes previously confirmed to play a role in polygenic susceptibility to NSV. Further studies are needed to clarify the exact role of HLA-DQB1 on NSV pathogenesis.

Nagashima-type palmoplantar keratoderma and malignant melanoma in Japanese patients

Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive type of PPK with non-progressive, diffuse, transgradient hyperkeratosis. Clinical findings usually include mild diffuse palmoplantar hyperkeratosis with well-demarcated diffuse erythema on the dorsal aspects of the hands and feet, forearms, elbows, Achilles tendon, and knees. This article is protected by copyright. All rights reserved.

The first case of multiple pilomatricomas caused by somatic mutations of CTNNB1 without any associated disorder

Pilomatricoma is a common benign epithelial tumor that originates from hair cells. The etiology of pilomatricomas remains to be fully elucidated, but stabilizing mutations in the beta-catenin gene (CTNNB1) have been reported to be involved in the formation of hair follicle-related skin tumors, including pilomatricomas [1]. Beta-catenin is a crucial component of the Wnt signal transduction cascade; mutations of CTNNB1 lead to beta-catenin accumulation in the cytoplasm, which, in turn, forms complexes by binding to transcription factors. These complexes enter the nucleus and promote cell proliferation and differentiation, resulting in the formation of pilomatricomas [2]. Pilomatricomas are often solitary lesions, but they can also occur as multiple lesions. Multiple pilomatricomas are often associated with autosomal dominant disorders, such as myotonic dystrophy and familial adenomatous polyposis (FAP), but can also be associated with Rubinstein-Taybi syndrome (RTS), Turner syndrome, Gardner syndrome, Sotos syndrome, Kabuki syndrome, and Constitutional mismatch repair deficiency (CMMR-D). However, in contrast to cases of solitary pilomatricomas, those of multiple pilomatricomas caused by CTNNB1 mutations are extremely rare. A 26-year-old Japanese man was referred to our department with a 12-year history of multiple skin tumors occurring on the face, trunk, and extremities. On physical examination, seven tumors—cutaneous and subcutaneous—were observed on both cheeks (Fig. 1A, B), the left side of the neck (Fig. 1C), left shoulder, left cubital fossa (Fig. 1D), and upper back (bilateral; Fig. 1E). Clinical and histological features of the seven tumors are listed in Table 1. Serum levels of calcium, phosphorus, and parathyroid hormone were within the respective normal ranges. His medical history was unremarkable, and there was no known family history of skin tumors. Diagnosis of multiple pilomatricomas was made by skin biopsy (Table 1, Nos. 4 and 7), and all the tumors were surgically removed. Subsequently, the patient was examined for associated genetic disorders, but no abnormalities, except for the tumors, were detected. Screening gastroscopy and colonoscopy findings were unremarkable. For genetic analyses, written informed consent was obtained from the patient, and genomic DNA was extracted from the resected tumors by using DNA Extraction from Paraffin-embedded Tissue (TaKaRa, Japan), according to the manufacturer’s protocol. DNA samples were amplified by polymerase chain reaction, and direct sequencing of the amplified fragment of exon 3 of CTNNB1 was performed using the ABI3130 Genetic Analyzer and GeneMapper Software 5 (both Applied Biosystems, CA, USA). Mutational analysis of CTNNB1 demonstrated that 3/7 tumors (Table 1, Nos.1, 3,