Noriko Umegaki-Arao

Unique clinical and serological features of bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors

Recently, several cases of bullous pemphigoid (BP) associated with the use of a dipeptidyl peptidase-4 (DPP-4) inhibitor, a type of antihyperglycemic drug, have been reported (DPP4i-BP).1,2 Béné reported a strong association between DPP-4 inhibitor use and the risk of BP.3 The juxtamembranous extracellular non-collagenous 16a (NC16a) domain of type XVII collagen (COL17, also termed BP180) is a major target epitope of autoantibodies in BP.4 A recent study found that BP cases whose autoantibodies bound to BP180 at regions other than NC16a exhibited a non-inflammatory phenotype with fewer erythemas. Intriguingly, half of these cases had taken DPP-4 inhibitors at the time of development of BP.5 In this study, we explored whether DPP4i-BP exhibited any unique clinical and serological features as suggested by the previous study. This article is protected by copyright. All rights reserved.

Identification of factors contributing to phenotypic divergence via quantitative image analyses of autosomal recessive woolly hair/hypotrichosis with homozygous c.736T>A LIPH mutation

Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is caused by mutations in LIPH. Homozygotes for the LIPH c.736T>A (p.C246S) mutation, the most prevalent genotype in Japanese patients, present varying degrees of hair loss; however, determinants of this phenotypic diversity remain elusive.

Case of dominant dystrophic epidermolysis bullosa with amniotic band syndrome.

IL-5 was markedly high 3 days before IVIG treatment (62.9 pg/mL; reference range, <3.9 pg/mL). The level was reduced very quickly to an undetectable level by day 3 of IVIG (Fig. 1). Although we cannot exclude a possible effect of increased systemic prednisolone, IVIG treatment seemed to lead to a reduction of both the serum levels of autoantibodies and IL5, which is related to the induction of circulating eosinophils. Previous reports indicated that IVIG binds to the Fc receptors on antigen-presenting cells, which may subsequently suppress the cytokine production of T cells, such as c-interferon and IL-5. Therefore, IVIG treatment may decrease both the serum IL-5 level and other T-cell-derived cytokines. To the best of our knowledge, this is the first report in which the serum level of IL-5 was reduced after IVIG treatment, which may be involved in the clinical efficacy of IVIG in BP at least in part.

Dermoscopy of pigmented invasive ductal carcinoma mimicking basal cell carcinoma

tures (clods) on a white background (Fig. 2b,c). In the first case these clods had an annular distribution (Fig. 2a). The histopathology showed features of rounded and velvety epidermal naevus (RAVEN). Clods are aggregates of keratinocytes or pigmented basaloid cells distributed irregularly in the basal layer of the epidermis surrounding the dermal papillae. The whitish areas correspond to acanthosis, papillomatosis and hyperkeratosis with elongated rete ridges. Clinically, RAVEN is characterized by coalescent hyperpigmented plaques with a rounded shape and velvety appearance and they differ from classic epidermal naevus by their polycyclic form and a flattening and fading of brown on the periphery, giving a blurred appearance. Clonal seborrhoeic keratoses (CSK) are smaller, oval, acquired lesions. Epidermal naevus and CSK share the same histopathology with RAVEN, but on dermoscopy, they have a globular pattern corresponding to well-defined nests of basaloid cells. Large brown circles (oval exophytic epidermal structures with a hyperchromic brown edge surrounding a hypochromic area), found in verrucous epidermal naevus, do not correspond to our cases, so we prefer the term clods.

Azathioprine-induced alopecia and leukopenia associated with NUDT15 polymorphisms

Azathioprine (AZA), a widely used immunosuppressant, can induce cytotoxic effects including myelosuppression and alopecia.1 Recent studies revealed that polymorphisms of NUDT15 are associated with thiopurine-induced alopecia and leukopenia.2-5 The frequency of NUDT15 polymorphisms in East and South Asians is high (22.6% and 13.6%, respectively).5 Thus, adverse event management during AZA treatment is essential for Asian populations with these polymorphisms. This article is protected by copyright. All rights reserved.

Identification of a human papillomavirus type 58 lineage in multiple Bowen's disease on the fingers: Case report and published work review

Human papillomavirus (HPV) has been detected in some cases of Bowens disease, particularly on the fingers and genitalia. HPV‐58 is classified as a high‐risk mucosal type and accounts for a high percentage of cervical cancer in Asia. Moreover, several HPV‐58 lineages, including sublineage A1, have a high prevalence in Asia. However, the nature of HPV‐58‐associated skin cancer is still unknown. Here, we report a case of a Japanese patient with multiple Bowens disease on the fingers. A 33‐year‐old man presented with multiple reddish‐brown scaly plaques on his left middle finger and right ring finger. All lesions were surgically excised, and the diagnosis of Bowens disease was made. We performed Sanger sequencing using DNA extracted from paraffin‐embedded samples and identified HPV‐58 sublineage A1. Additionally, we review previous reports on HPV‐58‐associated skin cancers, including our case, showing a high regional prevalence in Asia. Further studies would be needed to reveal the relationship between HPV‐58 lineages and carcinogenesis in the skin.

Linear keratinocytic epidermal nevi on trunk skin caused by a somatic FGFR2 p.C382R mutation

Dear Editor, Non-epidermolytic keratinocytic epidermal nevi (KEN) are caused by somatic mutations in genes associated with the RAS/mitogen-activated protein kinase (MAPK) pathway or phosphoinositide-3 kinase/AKT pathway. Several particular mutations of KRAS have been reported to cause sebaceous nevi on the face and scalp but KEN on the trunk. A 3-year-old girl exhibited brown papules on her right lower extremity at birth and later developed pebbly brownish plaques scattered along the lines of Blaschko in two regions: one distributed from the right axilla to the right side of the trunk and the other from the right groin to the right thigh (Fig. 1a,b). Several yellowish smooth papules were evident on the right ring and little fingers (Fig. 1c). No extracutaneous sign was evident. Biopsy of the right axillary lesion revealed marked papillomatous acanthosis with rete ridge elongation but without hyperkeratosis or granular degeneration (Fig. 1d,e). Examination of multiple step sections revealed that the lesions contained several small pseudohorn cysts within the epidermis but lacked immature follicles, sebaceous glands and large keratinous cysts (Fig. 1d,e). We obtained written informed consent from her parents according to the guidelines of the institutional review board of the Keio University School of Medicine, and performed nextgeneration sequencing using custom targeted exome sequencing panels of the HaloPlex Target Enrichment System (Agilent Technologies, Santa Clara, CA, USA) for genodermatoses. The target resequencing library was constructed from genomic DNA of the lesional epidermis separated from dermis via ex vivo dispase treatment of biopsied specimen. We identified a missense mutation in FGFR2 (NM_000141.4: c.1144T>C [p.C382R]) and several common variations in genes associated with KEN (Table S1). Sanger sequencing confirmed that the FGFR2 c.1144T>C mutation was present in the lesional epidermis but not in blood leukocytes (Fig. 1f); the other genetic variations were evident in both tissues (Table S1). Therefore, we diagnosed unilateral KEN caused by a somatic FGFR2 p.C382R mutation. The FGFR2 p.C382R mutation, which is suspected as an activating mutation, has been reported in papillomatous, pedunculated sebaceous nevi on the face and the scalp in two cases. Our case showed a partly resembling clinicopathological appearance, namely a pebbly appearance and a lack of hyperkeratosis, but lacked sebaceous differentiation. Such phenotypic differences associated with identical mutations at different body sites have also been reported in KRAS p.G12C and p.G12D mutations, which cause sebaceous nevi on the head but KEN on the trunk. Our case and previous cases suggest that FGFR2 p.C382R mutation triggers the development of sebaceous nevi on the head but KEN on the trunk, while another FGFR2 mutation of p.Y376C causes KEN both on the head and trunk (Table S2). Congenital FGFR2 p.Y376C

A case of adult T-cell leukemia/lymphoma presenting with erythema gyratum repens-like eruptions

Dear Editor, Adult T‐cell leukemia/lymphoma (ATLL) is a peripheral T‐cell malignancy caused by human T‐lymphotropic virus type I (HTLV‐1). Cutaneous involvement is common in ATLL with variable manifestations, including multiple papules, nodules, plaques, erythrodermas, and purpuric lesions. Erythema gyratum repens (EGR) is characterized by serpiginous “wood‐grain” or “zebra‐like” erythema, usually associated with an underlying malignancy. Here, we report a case of acute‐type ATLL presentingwith distinct EGR‐like eruptions, whichwas improved by combination therapywith injected interferon‐gamma and etretinate.

Distinct phenotype of epidermolysis bullosa simplex with infantile migratory circinate erythema due to frameshift mutations in the V2 domain of KRT5.

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Successful treatment of intractable vulvitis circumscripta plasmacellularis via combination therapy with topical tacrolimus and tetracycline

nodule implicates presence of granulomatous reaction in the tumor. After tick bite, R. japonica is first captured by the phagocytes including macrophages, and infects intracellularly, which may induce a granulomatous reaction. Fortunately, the present case recovered by oral cefcapene pivoxil. Presence but no significant elevation of the anti-R. japonica serological data implicates the patient’s prior infection to R. japonica. The circulating anti-R. japonica IgG binds to R. japonica, and might have induced the phagocytosis. The favorable outcome of the present case may be exceptional. Although the clinical manifestation of the present case was that of common superficial or deep skin infection, it is important for dermatologists to consider Rickettsia infection if an eschar appears around the wound.