Akira Kawada

Prurigo pigmentosa, Ketonemia and Diabetes mellitus

The etiology of prurigo pigmentosa still remains unknown. We present a 16-year-old female patient with ketonemia caused by diabetes mellitus. The eruption subsided when blood glucose and total ketone levels were controlled by subcutaneous insulin injection. We propose that ketonemia caused by diabetes mellitus may play a role in the pathogenesis of prurigo pigmentosa.

Contact sensitivity induced by neomycin with cross-sensitivity to other aminoglycoside antibiotics

1. Kaniwa M, Isama K, Nakamura A et al. Identification of causitive chemicals of allergic contact dermatitis using a combination of patch testing patients and chemical analysis. Contact Dermatitis 1994: 30: 26–34. 2. Lear J T, English J S C. Hand involvement in allergic contact dermatitis from mercaptobenzothiazole in shoes. Contact Dermatitis 1996: 34: 432. 3. Bruze M, Almgren G. Occupational dermatoses in workers exposed to resins based on phenol and formaldehyde. Contact Dermatitis 1988: 19: 272–277.

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.

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.

Contact dermatitis due to diethyl sebacate

zole, and between isoconazole and tioconazole (3, 11, 14). Cross-sensitivity has rarely been reported between clotrimazole and other structures, bifonazole and other structures, or ketoconazole (also a phenylethyl imidazole) and other structures (3). The case reported here is unique in that the patient showed positive reactions to croconazole and itraconazole, besides clotrimazole, and had apparently used only 1 azole. Croconazole, belonging to the phenmethyl imidazoles like clotrimazole, was first marketed in Japan and Korea in 1986 and was introduced to the European market only recently. There are a number of publications on hypersensitivity to it (8, 9, 21) and cross-sensitivity between croconazole, isoconazole, bifonazole, and clotrimazole was reported in 1988 (8). Croconazole seems to owe its position as the only strong sensitizer among the azole derivatives to its methylene group (7).

Leopard Syndrome Associated with Hyperelastic Skin: Analysis of Collagen Metabolism in Cultured Skin Fibroblasts

We present a patient with Leopard syndrome and hyperelastic skin. Biochemical analysis using cultured skin fibroblasts showed normal type III and V collagen synthesis, lysyl hydroxylation level of type I procollagen and processing of pro-α1 and α2(I). Our results suggest that molecular defects of hyperelasticity in Leopard syndrome are not related to abnormal collagen metabolism, although not all steps of collagen synthesis have been investigated.

Cathepsin D expression in skin metastasis of breast cancer

Cathepsin D, an aspartic proteinase, correlates with invasion and metastasis in breast cancer and with poor prognosis. In the present study, we examined the immunohistological expression of cathepsin D in both primary (5 cases) and skin‐metastatic breast cancers (13 cases) and compared it to those in gastric (2 cases) and lung (4 cases), and primary eccrine cancers (3 cases). All breast and gastric cancers were adenocarcinomas. The 2 gastric cancers were poorly differentiated, while the 4 lung cancers consisted of 2 poorly differentiated adenocarcinomas, 1 poorly differentiated large cell carcinoma, and 1 moderately to poorly differentiated squamous cell carcinoma. We also surveyed the immunohistological distribution of cathepsin B, carcinoembryonic antigen, gross cystic disease fluid protein‐15, c‐erbB‐2, and estrogen receptor. In almost all breast cancer samples, the cancer cells demonstrated strong expression of cathepsin D in the cytoplasm, but weak staining patterns with other antibodies. Gastric and lung cancer cells did not respond with cathepsin D (except one metastatic lung cancer) or the other immunohistological markers. Since cathepsin D is strongly expressed in primary and metastatic lesions of breast cancer, cathepsin D could be useful as an adjunct to a panel of immunohistochemical stains in determining the primary site of origin of metastatic cancer in the skin.

Drug eruption due to bucillamine

A 56-year-old woman had had rheumatoid arthritis (RA) for over 30 years, and received drug therapy (loxoprofen and sofalcone) in our hospital for 7 months. She was seen in June 1997 with red papules on the face, neck and arms that had started a few days before. She had been taking bucillamine (RimatilA, Santen, Osaka, Japan) 100 mg q.d.s. orally for 2 weeks, in addition to loxoprofen 60 mg t.d.s. and sofalcone 50 mg t.d.s. We performed patch tests with 20, 10, 1, and 0.1% pet. bucillamine. 20 and 10% pet. bucillamine produced erythema and papules with pruritus at D2 and D3, and 1% pet. bucillamine produced red papules with pruritus at D3, but 0.1% pet. showed no response. Moreover, patch tests carried out with 20, 10, 1, and 0.1% pet. penicillamine produced no erythema or papular response at D2 and D3. Patch tests with 30 and 10% pet. bucillamine in 8 normal subjects showed erythema and papules at D2 and D3 in 3 subjects, and patch tests with 1 and 0.1% pet. bucillamine in these 8 subjects showed no erythema or papular response at D2 and D3. LST (lymphocyte stimulation test) with bucillamine was negative.

Drug eruption due to flavoxate hydrochloride

on her eyelids (Fig. 1). She did not use eyelash curlers or any other cosmetics, but had applied an eyelid paste on her upper eyelids every morning for 2 years for cosmetic purposes. The dermatitis disappeared soon after discontinuing the eyelid paste application followed by treatment with topical corticosteroid. Patch testing with an occlusion time of 2 days on her back gave positive reactions on days 3, 4, and 7 to the eyelid paste (as is) and its chief ingredient (50% v/v) natural rubber latex (NRL) (low ammonia, 10% pet.). No reactions were detected to parabens, fragrances or other ingredients, including rubber additives and pre-

Characteristics of UVA-Induced Delayed Tanning: Seasonal Variation

We studied seasonal variation in UVA‐induced delayed tanning and compared it to that in UVA + B‐induced delayed tanning. The minimal tanning dose (MTD) and the minimal melanogenic dose (MMD) were determined one week after UVA exposure or UVA + B exposure, respectively. The MTD determined in the summer (June to August) was significantly higher than that in winter (December to February). In addition, while MTD in the winter correlated well with skin color, there was no correlation between MTD and skin color in summer. MTD tended to correlate with self‐reported tanning history at the initiation of tanning in the winter, but they were not correlated with each other in the summer. The MMD measured in the summer was significantly lower than that in the winter. MMD correlated well with skin color in both seasons; the lighter the skin, the smaller the MMD. Also, a correlation was detected between MMD and self‐reported tanning history. These results suggest that the susceptibilities of delayed tanning to UVA and UVA + B are affected by different factors.