R. Osawa

Filaggrin Gene Defects and the Risk of Developing Allergic Disorders

Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and have been shown to be major predisposing factors for atopic dermatitis (AD). Approximately 40 loss-of-function FLG mutations have been identified in patients with ichthyosis vulgaris (IV) and/or atopic dermatitis (AD) in Europe and Asia. Major differences exist in the spectra of FLG mutations observed between different ancestral groups. Notably, prevalent FLG mutations are distinct between European and Asian populations. Many cohort studies on FLG mutations in AD have revealed that approximately 25-50% of AD patients harbour filaggrin mutations as a predisposing factor. In addition, FLG mutations are significantly associated with AD-associated asthma. The risk for developing allergic rhinitis is also significantly higher with a FLG mutation, both with and without accompanying AD. Recent studies have hypothesized that skin barrier defects caused by FLG mutations allows allergens to penetrate the epidermis and to interact with antigen-presenting cells, leading to the development of atopic disorders including asthma. The restoration of skin barrier function seems a feasible and promising strategy for prophylactic treatment of AD patients with FLG mutations.

Radiotherapy for extramammary Paget's disease: histopathological findings after radiotherapy

Summary Several reports have suggested the efficacy of radiotherapy for treating extramammary Pagets disease (EMPD); however, these reports comprised only clinical observations, without in‐depth histopathological observations. We report our experience of genital EMPD treated by radiotherapy in two elderly women, and the marked efficacy of radiotherapy, confirmed both by clinical observation and by detailed histopathological investigations. Our cases agree with the notion that radiotherapy is useful as an alternative therapy for EMPD, and should be considered particularly in elderly patients who may not tolerate surgery well.

Naevus sebaceus on the female breast accompanied with a tubular apocrine adenoma and a syringocystadenoma papilliferum

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Primary cutaneous CD30+ anaplastic large‐cell lymphoma with generalized skin involvement and involvement of one peripheral lymph node, successfully treated with low‐dose oral etoposide

Primary cutaneous CD30+ anaplastic large‐cell lymphoma (PCALCL) in adults is rare, and the prognosis is generally excellent. Multifocal PCALCL tends to relapse after multiagent chemotherapy and is generally considered more prone to progress to extracutaneous involvement than is the localized disease. We report a 43‐year‐old woman with PCALCL who had generalized skin involvement accompanied by involvement of one peripheral draining lymph‐node region. Although the disease relapsed after multiagent chemotherapy regimens, the disease was successfully treated with low‐dose etoposide. We reviewed the previously reported cases of PCALCL treated with low‐dose etoposide. We suggest that oral etoposide might be a useful effective treatment for treatment of relapsed multifocal PCALCL.

Bullous pemphigoid associated with dermatomyositis and colon carcinoma.

It has been suggested that both bullous pemphigoid (BP) and dermatomyositis are associated with internal malignancies. However, there are no reports of the coexistence of these three conditions in one patient. We report the first case, to our knowledge. of coexistent BP, dermatomyositis and colon carcinoma. An 81‐year‐old Japanese woman was diagnosed with dermatomyositis based on muscular weakness and tenderness of the extremities, increased levels of circulating muscle enzymes and histological inflammatory changes in skeletal muscle and skin. Carcinoma of the sigmoid colon was detected during screening for internal malignancy; she was therefore surgically treated. Ten days after the operation, several large bullous eruptions appeared on her extremities. From the histopathological, immunofluorescence microscopy and BP180 ELISA study findings, we diagnosed the bullous eruptions as BP. Coexistence of BP with dermatomyositis or colon carcinoma is rare. Although the reason why our case exhibited these three disorders is not understood, it is suggested that these conditions may be associated with epitope spreading.

Extremely severe palmoplantar hyperkeratosis in a generalized epidermolytic hyperkeratosis patient with a keratin 1 gene mutation

To the Editor: Epidermolytic hyperkeratosis (EHK; OMIM#113800), also called bullous congenital ichthyosiform erythroderma, is a rare genetic disorder of keratinization. We report a patient with generalized EHK showing extremely severe palmoplantar hyperkeratosis with digital contractures. A 45-year-old Japanese man had erythroderma at birth. He exhibited skin blistering, erosions, and hyperkeratosis on the erythrodermic skin since infancy. The blistering and erosions gradually diminished with age. He developed severe palmoplantar hyperkeratosis and digital contractures at 7 years of age. At 24 years of age, surgery was performed to improve the contraction of his toes. A physical examination revealed hyperkeratosis of the entire body, especially at the ankles, elbows, and knees, and erosions were observed on the inner side of the elbows and knees (Fig 1, A-D). Palmoplantar hyperkeratosis was severe with digital contractures. The

Punctate palmoplantar keratoderma type 1: a novel AAGAB mutation and efficacy of etretinate.

Punctate palmoplantar keratoderma type 1 (PPKP1, OMIM#148600), also known as the Buschke-FischerBraurer type, is a rare form of palmoplantar keratoderma that is autosomal dominantly inherited (1). PPKP1 is clinically characterised by multiple punctate hyperkeratotic papules affecting the palmar and plantar skin, with considerable phenotypic variation among patients (2). These circumscribed papules gradually coalesce and increase in number with age (2). The lesions typically start to appear in early adolescence but sometimes develop later in life. In 2012, linkage analysis and whole-exome sequencing identified heterozygous null mutations within AAGAB as a cause of PPKP1 (2, 3). AAGAB encodes αand γ-adaptin binding protein p34, which is involved in clathrin-mediated vesicle transport (2). Loss-of-function mutations in AAGAB result in haploinsufficiency of p34 (2). To date, 20 AAGAB null variants have been identified in Scottish, Irish, English, German, Tunisian, Chinese Mexican and Japanese populations (2–8). Here we report a Japanese case with PPKP1 carrying a novel AAGAB null mutation.

A case of Bockenheimer's syndrome (genuine diffuse phlebectasia): venous involvement inside muscles was detected by magnetic resonance imaging

We report a 13‐year‐old girl with an extensive bluish phlebectasia of the upper right arm and right side of the chest, which had been present since birth. There was no difference in length between the right (affected) and left (healthy) limbs, but the involved limb was thicker than the noninvolved limb. Magnetic resonance imaging showed distended veins with slow blood flow under the skin of the right limb. The veins inside the muscles of forearm were also involved. Histological examination of the bluish lesions revealed large phlebectasia showing distended veins without any proliferation of endothelial cells. The amount of elastin in the walls of these veins was decreased. The patient was diagnosed with Bockenheimers syndrome. The characteristics of this rare syndrome are indicated and discussed.

Widespread erythema ab igne caused by hot bathing.

appropriate treatment without waiting for the conventional mycological examination. In contrast, conventional fungal cultures require long incubation periods of 1–5 weeks and optical microscopy is usually performed with a particular staining such as KOH or blue lactophenol with an incubation of around 10–30 min to increase its sensitivity. In vivo RCM has the additional advantage, compared to conventional optical microscopy and cultures, of being non-invasive and not limited to the analysis of the extracted hair, being able to explore the entire lesion, thus reducing false negative cases. However, in vivo examination cannot be performed in case of suppuration or crusting that give artefacts. Ex vivo RCM examination avoids the problem of movements in children and is not very invasive because the collection of the hair, in case of hair dermatophytosis due to the parasitic involvement, is usually not painful. In conclusion, this study shows that RCM can identify hair dermatophytes and that conidia are ‘visible’ under RCM due to their high reflectance. Further studies are needed to define the RCM features of different types of dermatophytes and to compare RCM performances with the conventional techniques. Although at present RCM cannot replace the current diagnostic standards for hair dermatophytosis, it may be successfully used as an additional tool to facilitate the diagnosis and indicate the need for further investigation of the patient.

Characteristic findings of handprint and dermoscopy in reticulate acropigmentation of Kitamura.

nism could involve impaired antigen-specific humoral immunity. However, PNP is very rare, and the association with HIV in our patient could have occurred by chance. Our patient initially presented with clinical and histological features consistent with a lichenoid drug eruption progressing to TEN. PNP can be diagnostically challenging, and this case emphasizes the importance of considering this diagnosis in patients with severe, unresponsive mucocutaneous blistering. This is especially important in the context of HIV, given the increased frequency of drug eruptions owing to changing drug regimens and polypharmacy in individuals with this condition.