Megumi Mizawa

Expression of filaggrin-2 protein in the epidermis of human skin diseases: a comparative analysis with filaggrin.

Filaggrin-2 is a member of the S100 fused-type protein family, and the structural features and expression of filaggrin-2 are similar to those of profilaggrin, a protein essential for keratinization. In the present study, we investigated the expression profile of filaggrin-2 in patients with skin diseases using antibodies against the repetitive region of filaggrin-2. In tissue samples from patients with skin diseases which are associated with a decrease in filaggrin, including ichthyosis vulgaris, atopic dermatitis and psoriasis vulgaris, the expression level of filaggrin-2 was markedly decreased compared to that in normal skin samples. In contrast, the expression of filaggrin-2 increased in parallel with that of filaggrin in samples of tissue from patients with skin diseases associated with hyperkeratosis, such as lichen planus and epidermolytic ichthyosis. Interestingly, filaggrin-2 signals were observed in slightly higher layers of the epidermis in comparison to those of filaggrin. Similarly, the expression of filaggrin-2 proteins was induced slightly later than filaggrin in the cultured keratinocytes. These findings suggest that filaggrin-2 may play an overlapping role with filaggrin in epithelial cornification; however, it may also have a partially distinct role in the molecular processes of cornification.

Stress Evaluation in Adult Patients with Atopic Dermatitis Using Salivary Cortisol

The symptoms of atopic dermatitis (AD) are often aggravated by stress, and AD can also lead to psychological stress due to social isolation and discrimination. The salivary cortisol level reflects psychological stress, and it is a good index to assess chronic stress. In this study, we measured the salivary cortisol levels in patients with AD (n = 30) and compared them with those of healthy control subjects (n = 42). AD patients were also evaluated for general disease severity using the Scoring Atopic Dermatitis (SCORAD) index. The serum levels of TARC, total IgE, and lactate dehydrogenase (LDH) and peripheral blood eosinophil counts were measured by laboratory tests. The Skindex-16 was used as a skin disease-specific, quality of life measure, instrument. The results showed that the saliva cortisol level was significantly higher in AD patients compared to healthy subjects (P < 0.01). The salivary cortisol level was significantly correlated with the SCORAD index (r = 0.42, P < 0.05) while the serum TARC and LDH levels were positively correlated with the SCORAD index. However, no statistically significant correlations were observed between the salivary cortisol level and Skindex-16. These results suggest that the saliva cortisol level is therefore a useful biomarker to evaluate the stress in AD patients.

Decreased filaggrin‐2 expression in the epidermis in a case of pityriasis rotunda

1 Kacar SD, Ozuguz P, Bagcioglu E et al. The frequency of body dysmorphic disorder in dermatology and cosmetic dermatology clinics: a study from Turkey. Clin Exp Dermatol 2014; 39: 422–38. 2 Philips KA, Hollander E, Rasmussen SA et al. A severity rating scale for body dysmorphic disorder: development, reliability, and validity of a modified version of the Yale-Brown Obsessive Compulsive Scale. Psychopharmacol Bull 1997; 33: 17–22. 3 Mufaddel A, Osman OT, Almugaddam F, Jafferany M. A review of body dysmorphic disorder and its presentation in different clinical settings. Prim Care Companion CND Disord 2013; 15: pii: PCC.12r01464. 4 Coneicao Costa DL, Chagas-Assuncao M, Arzeno Ferrao Y et al. Body dysmorphic disorder in patients with obsessivecompulsive disorder: prevalence and clinical correlates. Depress Anxiety 2012; 29: 966–75. 5 Phillips KA, Wilhelm S, Koran LM et al. Body dysmorphic disorder: some key issues for DSM-V. Depress Anxiety 2010; 27: 573–91.

Incomplete erythropoietic protoporphyria caused by a splice site modulator homozygous IVS3‐48C polymorphism in the ferrochelatase gene

Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by both the partial deficiency of ferrochelatase (FECH) and the existence of cytosine at IVS3‐48 in trans to a mutated FECH allele. However, physicians occasionally encounter patients with EPP with a mild phenotype associated with a slight increase in the erythrocyte‐free protoporphyrin concentration and no FECH gene mutations. In this study, genetic analyses were performed on three patients with a mild phenotype of EPP, with photosensitivity, slightly increased erythrocyte‐free protoporphyrin concentrations and only a few fluorocytes in the peripheral blood. After obtaining the patients’ and their parents’ informed consent, a direct sequence analysis of the FECH gene and a restriction fragment length polymorphism analysis were performed on samples from the patients. The FECH gene mutation was not detected in the direct sequence analyses in any of the patients. However, all three patients had the homozygous IVS3‐48C polymorphism. These findings suggest that homozygous IVS3‐48C polymorphism of the FECH gene is associated with a slight elevation of the protoporphyrin level in erythrocytes, resulting in a mild EPP phenotype.

Effectiveness of Keishibukuryogan on Chronic-Stage Lichenification Associated with Atopic Dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease with recurring episodes of itching and a chronic relapsing course. Keishibukuryogan (KBG) is a traditional herbal medicine, composed of five kinds of medical plants and has been administered to patients with blood stagnation in Japan. This study investigated the effect of KBG on the disease activity in AD (n = 45) patients. AD patients were administered KBG for 4 to 6 weeks in addition to their prescribed medications. The results showed that the SCORAD index and VAS score were significantly decreased after the administration of KBG (P < 0.01). KBG also decreased the serum LDH level significantly (P < 0.01). The global assessment of the clinical response in SCORAD index showed that 88.5% of the patients with moderate improvement to excellent response (n = 26) had a high lichenification score (lichenification score ≥2 in SCORAD). On the other hand, only 42.1% of the patients with no improvement to mild improvement (n = 19) had a high lichenification score. Furthermore, long-term administration of KBG for 9–67 weeks showed a marked improvement in patients with a high lichenification score. Therefore, KBG was found to be effective against AD, particularly in cases presenting with lichenified lesions.

Immunohistological examination of a skin lesion in a Japanese case with hand, foot and mouth disease caused by coxsackie-virus A6

Hand, foot and mouth disease (HFMD) is a self-limited and highly contagious viral infection that most commonly occurs in children. Serious outbreaks of HFMD occurred in Taiwan, Singapore and Finland in 2008 [1-3] and most recently in Japan in 2011 [4]. This epidemic was caused by coxsackievirus A6 (CVA6). CVA6-induced HFMD is known to present with atypical clinical manifestations [5-7]. This report describes the results of an immunohistochemical examination of a skin lesion in a Japanese adult with [...]

Induction of Skin Lesions by Ultraviolet B Irradiation in a Case of Pemphigus Erythematosus

© 2014 The Authors. doi: 10.2340/00015555-1781 Journal Compilation

The expression profile of filaggrin-2 in the normal and pathologic human oral mucosa

The epithelial cells of the oral cavity show a remarkable degree of regional variation with respect to their morphology and keratinization status. In the oral cavity, the tongue and palate contain keratinizing stratified epithelia, while the buccal mucosa contains non-keratinizing stratified epithelia. We herein examined the expression of filaggrin-2, a member of the S100 fused-type protein family, in the oral mucosa. Filaggrin-2 was weakly expressed in the normal epithelium of the palate, but not in the buccal mucosa or tongue, although filaggrin protein was observed in the epithelium of the buccal mucosa and the palate. We next examined the expression of filaggrin-2 in the oral mucosa of subjects with hyperkeratotic diseases. The expression of filaggrin-2 was markedly increased in the epithelium of the oral mucosa in patients with lichen planus, leukokeratosis and leukoplakia. Filaggrin-2 positivity was observed in granules, some of which were co-localized with those of filaggrin. These results indicate that filaggrin-2 was expressed in the oral mucosa under certain pathological conditions, demonstrating that an aberrant protein expression, together with filaggrin, indicates the altered differentiation program including hyperkeratosis that occurs in these diseases.

Jumihaidokuto (Shi-Wei-Ba-Du-Tang), a Kampo Formula, Decreases the Disease Activity of Palmoplantar Pustulosis

Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by sterile intraepidermal pustules associated with erythematous scaling on the palms and soles. Jumihaidokuto is a traditional herbal medicine composed of ten medical plants and has been given to patients with suppurative skin disease in Japan. This study investigated the effect of jumihaidokuto on the disease activity in PPP patients (n = 10). PPP patients were given jumihaidokuto (EKT-6; 6.0 g per day) for 4 to 8 weeks in addition to their prescribed medications. The results showed that the palmoplantar pustular psoriasis area and severity index (PPPASI) was decreased after the administration of jumihaidokuto (p < 0.05). Therefore, Jumihaidokuto is seemingly effective against PPP.

Primary cutaneous Ewing sarcoma following metastasis to the bone and lymph nodes

nomenclature of these three syndromes. However, avoidance of eponyms has become the public tendency in recent years and an acronym is preferred which summarizes information of the disease. Nevertheless, the acronyms JMP and CANDLE seem to represent only limited aspects of this disease, the advanced phenotypes and the pathological features, respectively. Indeed, Online Mendelian Inheritance in Man (OMIM) #256040, in which the designation ‘Nakajo syndrome’ has long been registered until recently, now includes all three syndromes under the new designation ‘autoinflammation, lipodystrophy and dermatosis (ALDD) syndrome’. Furthermore, a new conceptual acronym ‘proteasome-associated autoinflammatory syndromes (PRAAS)’ has recently been proposed as the umbrella term for these three syndromes. However, to apply this designation, proteasome dysfunction due to the novel mutation should be evident. Collectively, we believe that it would be both appropriate and desirable to discuss the distinction of these syndromes from the genetic and clinical aspects and, if they are really included in the same entity, to select the most suitable designation for the definition.