Itsuro Matsuo

Oesophageal involvement in pemphigus vulgaris

Oesophageal involvement of pemphigus vulgaris had been considered an exceptional event. However, our endoscopic study found oesophageal lesions in seven of eight (87.5%) patients with pemphigus vulgaris.

Formation of cornified cell envelope in human hair follicle development

Summary Background Cornified cell envelope (CCE) formation is an important step in the final stage of keratinization, in which CCE precursor proteins including involucrin and loricrin are cross‐linked by keratinocyte transglutaminases (TGases) to the inner surface of the plasma membrane of cornified cells, while the outer surface is coated with material derived from secreted lamellar granules.

Carcinomatous transformation of eccrine syringofibroadenoma

Background: While squamous cell carcinoma and pseudocarcinomatous hyperplasia have been documented as pre‐existing lesions in cases of reactive eccrine syringofibroadenoma (ESFA), to the best of our knowledge carcinoma occurring in a solitary ESFA has not yet been reported. We present one such case in a 91‐year‐old female who had a dome‐shaped, reddish tumor on the extensor side of the left forearm.

In vitro phototoxicity of new quinolones: production of active oxygen species and photosensitized lipid peroxidation

To elucidate photosensitization potentials of new quinolone antibacterial agents, production of active oxygen species and peroxidation of squalene after ultraviolet A exposure were investigated. Production of singlet oxygen and/or hydrogen peroxide was estimated by bleaching of p‐nitroso‐N, N‐dimethylaniline. Lomefloxacin showed the greatest ability to produce active oxygen species, and this ability was reduced by the addition of the singlet oxygen quencher sodium azide. Ciprofloxacin and fleroxacin also had strong activity. Photosensitized peroxidation of squalene was evaluated by measurement of thiobarbituric acid‐reactive substances. Lomefloxacin was the strongest sensitizer, followed by fleroxacin and ciprofloxacin. These results suggest that certain new quinolones are involved in phototoxicity via the mechanism of active oxygen species.

Human Papillomavirus Associated with Bowen's Disease of the Finger

We report here a case of Bowens disease that developed in the periungual area of the left ring finger of a 55‐year‐old Japanese male. Because the histology of the lesion mimicked in part the features of a common wart, a PCR‐based analysis of human papillomavirus (HPV) DNA and sequencing of viral DNA of PCR‐amplified fragments were performed. The lesion contained HPV11 and 16 DNA, and HPV was suspected to play a role in the development of the lesion.

Pemphigus erythematosus: Detection of Anti-Desmoglein-1 Antibodies by ELISA

Kawakami et al. [1] report on 2 patients with ichthyosis and mental retardation, who are diagnosed as having (incomplete) Sjögren-Larsson syndrome (SLS). We disagree with the authors. The SLS is a highly characteristic neurocutaneous disorder with congenital ichthyosis, spasticity, mental retardation and retinal glistening dots [2–4]. The ichthyosis is generalized, with the trunk, flexures and the dorsal aspects of hands and feet the most severely affected sites. The ichthyotic skin is colored yellowish-brown and gives rise to pruritus. Spasticity and mental retardation are severe, but not progressive, in most cases. SLS is caused by a deficiency of microsomal fatty aldehyde dehydrogenase (FALDH) that catalyzes the conversion of mediumand long-chain fatty aldehydes to their corresponding fatty acids [5]. The FALDH gene has been identified, and mutations have been found in this gene in SLS patients. Curative treatment strategies are not available. The ichthyosis in the patients described by Kawakami et al. [1] differs from the ichthyosis seen in SLS, as the authors state themselves. Mental retardation is the only additional feature in both patients; however, its severity is not mentioned in patient 1, while it is reported to worsen gradually in patient 2. Spasticity and retinal glistening dots are present in the vast majority of SLS patients but are not found in patients 1 and 2. Biochemically, FALDH activity in patient 2 is in the range of SLS heterozygotes. Patient 2 is reported to have the same level of FALDH activity, but no quantitative data are given. Contrary to the statement of the authors, partial enzyme deficiency has never been reported in SLS patients, especially not in their references 2, 19, 20 and 21 [6–9]. Moreover, it has been established that SLS heterozygotes, i.e. carriers of FALDH deficiency, are asymptomatic [9]. The clinical features in patients 1 and 2 do not resemble SLS, and their FALDH activity is above the upper limit of SLS homozygotes. Taken together, these data indicate that the diagnosis of (incomplete) SLS is highly unlikely both on clinical and biochemical grounds. A more plausible explanation for the biochemical findings in these patients is that one of the parents is an asymptomatic carrier of FALDH deficiency and that the same heterozygous state, not explaining the clinical features, has been demonstrated in both patients. Parental FALDH activities should be measured and reported additionally, to close the controversy. Furthermore, molecular analysis which can now be done routinely in various centers including our own, should be performed. Dietary therapy with medium-chain triglycerides has been demonstrated to be ineffective in SLS [10]. This fact, and not the patients’ development delay, should be the reason for not performing dietary therapy in SLS. In conclusion, we object to the diagnosis of (incomplete) SLS in the patients described by Kawakami et al. [1]. A diagnosis of SLS, including so-called atypical or incomplete SLS, has to be proven by demonstrating a FALDH activity in the range of SLS homozygotes. Dietary therapy with medium-chain triglycerides should not be performed in SLS patients.

Structural, enzymatic and molecular studies in a series of nonbullous congenital ichthyosiform erythroderma patients

Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immunohistochemical and ultrastructural observations, transglutaminase activity assays and sequencing of TGM1 were performed in five patients from four NBCIE families. Transglutaminase 1 (TGase 1), involucrin and loricrin expression and in situ transglutaminase activity were present in all of the cases. Ultrastructurally, two cases out of five showed incomplete thickening of the cornified cell envelope (CCE) during keratinization and the other three exhibited abnormal lipid droplets in the cornified cells and malformed lamellar granules. No TGM1 mutation was found in any of the four families by direct sequence analysis. NBCIE cases with normal TGase 1 seemed to have two distinct patterns of abnormality, one with abnormal lipid droplets and malformed lamellar granules and the other with defective CCE formation.

Extraordinarily Large Calcifying Epithelioma without Aggressive Behavior

Calcifying epithelioma was first described by Malherbe and Chenantais [1] in 1880 and was renamed ‘pilomatrixoma’ by Forbis and Helwig [2] in 1961. Calcifying epithelioma usually appears as a benign, subcutaneous tumor, less than 3 cm in size. However, in the 1970s, remarkably large calcifying epitheliomas showing malignant potential were reported as ‘giant calcifying epithelioma’ [3, 4]. We report here a case of calcifying epithelioma, extraordinarily large in size, with no observable malignant histopathological feature or biological aggressive behavior. A 23-year-old man was referred to our dermatology clinic, chiefly complaining of a tumor on the left upper arm. One year before presentation, the patient had noticed an asymptomatic, solitary, normalcolored papule which had since grown gradually. On examination, the patient had an asymptomatic, dome-shaped, pink to reddish tumor, 6 cm in diameter, on the extensor side of the left upper arm (fig. 1a). The overall tumor was soft, although firm in part. CT scan revealed a soft tissue density mass in the subcutaneous tissue, with no invasion or infiltration of the tumor into the underlying muscles and bones (fig. 1b). The tumor was completely resected and histopathological examination showed that the tumor consisted of nests of eosinophilic shadow cells and basophilic cells in the dermis (fig. 2). Cystic structures were seen in the tumor. The margin of the tumor was clearly demarcated with a fibrous capsule, and no invasion or infiltration of the tumor cells into the underlying tissues including muscles was seen. Neither atypism nor abnormal mitotic figures of the tumor cells were observed. On the basis of these findings, the tumor was diagnosed as a calcifying epithelioma, even though its size was extremely large. Five months after the operation, neither local recurrence nor metastasis was observed.

Pyridoxine-Induced Photosensitivity and Hypophosphatasia

We describe a case of photosensitivity due to pyridoxine hydrochloride (vitamin B6) in a heterozygote of hypophosphatasia. Photopatch tests using pyridoxine hydrochloride and pyridoxal 5′-phosphate, compounds referred to as vitamin B6, with ultraviolet light A irradiation were positive. Laboratory examination showed low serum alkaline phosphatase. Tissue-nonspecific alkaline phosphatase exon amplification from DNA of the patient’s lymphocytes detected deletion 1154–1156 hypophosphatasia mutation, indicating that this patient was diagnosed to be a heterozygote of hypophosphatasia. The seric pyridoxal 5′-phosphate level of this patient with hypophosphatasia was higher than in normals. Furthermore, after oral administration of vitamin B6 this level increased greatly and long-lastingly, and this might be related to the low level of alkaline phosphatase in this patient. Photosensitivity in this patient may have been caused by abnormal metabolism of vitamin B6 under the hypophosphatic condition.