Recent advances in the investigations of the molecular basis of hypohidrotic ectodermal dysplasia (HED) and incontinentia pigmenti (IP) are reviewed. A new member of TNF-ligand, ectodysplasin (EDA), its receptor, EDAR, and EDAR-associated death domain (EDARADD), have been isolated. Mutations of these genes have been identified as the cause of X-linked and autosomal forms of HED. NEMO/IKKγ gene deficiency has been shown to cause IP. Recent reports have elucidated that HED and immunodeficiency (HED-ID) is also derived from mutations in exon 10 of the NEMO/IKKγ gene. These data not only confirm the important role of EDA/EDAR signal trunsduction in regulating the morphogenesis of the ectoderm but also provide the unique view that NF-κB activation through NEMO/IKKγ is crucial in the development of skin appendages and the immune system.
We reviewed 28 cases of creeping eruption seen in our department during the last six years. The cases consisted of 16 male and 12 female patients, and the average age was 50. About 90% (25 out of 28 cases) visited our outpatient clinic from November to January. This is the period when raw icefish is frequently eaten in Akita prefecture. Seventy five percent (21 cases out of 28) of the patients had eaten raw icefish caught in the Hachirougata Lagoon. These findings suggest that the major cause of creeping eruption in Akita might be the consumption of raw icefish.
Eleven patients with malignant melanoma metastatic to the liver were treated with hepatic arterial chemoembolization using cisplatin and gelatin sponge. Nine cases had ocular melanoma, and two had cutaneous melanoma as the origin. In all the cases, multiple tumor metastases were already present when they were detected initially. The dose of cisplatin was set at 70 mg/m2. Complete response of the tumor was observed in one patient and partial response was observed in the two other patients (response ratio: 23.0%). The median survival for the entire group was 14 months. Upper abdominal pain, appetite loss, nausea, and elevation of liver enzymes were observed as treatment related morbidity factors but lasted briefly. Elevation of lactate dehydrogenase (LDH) before chemoembolization was the only statistically significant poor prognostic factor (p=0.0044, Log-rank test). Hepatic arterial chemoembolization prolonged survival time with less treatment-related morbidity among these melanoma patients with multiple metastases to the liver.
The increasing use of topical NSAIDs for inflammatory lesions has caused a number of cases, mainly of photocontact dermatitis. Prolonged photosensitivity has been often observed in ketoprofen-induced photocontact dermatitis long after stopping contact to the causative agent. We examined phototoxicity, photosensitivity and the mechanism of prolonged photosensitivity to NSAIDs using guinea pigs. Ketoprofen (Mohrusr®), felbinac (Seltouch®) and flurbiprofen were tested. Tetrachlorosalicylanilide (TSCA) was used as positive control. Cyclophosphamide was used in some experiments as an immunoadjuvant to enhance the sensitization. No animals showed phototoxic reactions to ketoprofen, felbinac and flurbiprofen. Photoallergic contact sensitization was induced in all animals tested with 40% ketoprofen, 5% ketoprofen and 2% TSCA. Furthermore in photosensitized animals with ketoprofen, eczematous lesions were elicited with only ultraviolet A (UVA) irradiation even 42 days after topical application of the sensitizer. On the other hand, felbinac and flurbiprofen did not induce photoallergic contact sensitivity even with pretreatment by cyclophosphamide. These experimental results suggest that felbinac or flurbiprofen is safer than ketoprofen for topical use to the sun-exposed areas.
Pemphigus is clinically divided into three subtypes : pemphigus vulgaris with a dominant mucosal lesion (PV-M), mucocutaneous lesion (PV-MC), and typical pemphigus foliace (PF). Several cases have changed clinical phenotypes among the three pemphigus phenotypes during the in clinical courses. Mean while a novel enzyme-linked immunosorbent assay (ELISA) with recombinant desmoglein (rDsg1) and rDsg3 has been developed as a highly sensitive and specific diagnostic tool for pemphigus. We experienced three cases undergoing clinical transition from PV-MC to PF, eight cases from PV-MC to PV-M, and one case from PV-M to PVMC. Their sera were obtained and the anti-Dsg antoantibody titers were analysed using ELISA. The clinical changes were clearly associated with the change of autoantibody profile from Dsg3+/1+ to Dsg3–/1+, from Dsg3+/1+ to Dsg3+/1–, and from Dsg3+/1– to Dsg3+/1+, respectively, confirming that the clinical transition among the three pemphigus phenotypes correlates well with changes in the titers of either anti-Dsg1 or anti-Dsg3 autoantibodies, We conclude that it is advantage to perform the Dsg ELISA during the time course of this disease, because we can promptly and accurately catch any transformation among the pemphigus phenotypes.
We report three cases of solar purpura (SP), which has been reported as a rare condition showing petechiae after the intense sun exposure. All three cases developed pinpoint-sized, purpuric eruptions after intense sun exposure with or without papular or macular erythematous eruptions. These purpuric eruptions were reproduced by UVB photoprovocation tests in all three cases. Although the mechanisms of this peculiar form of photosensitivity still remain unclear, photo-induced products might play some role in the induction of endothelial cell damage, resulting in extravasation of red blood cells.
Case 1: A 67-year old man presented with a purpuric nodule on his parietal region. The histopathological diagnosis was angiosarcoma. Treatment included local injection of IL-2, tumor excision, and radiation. After these treatments, 180 mg/m2 of paclitaxel was administrated twice at three week intervals, resulting in an decrease in leukocyte count and myalgia/arthralgia. We have been following him in our outpatient clinic. No recurrence or metastasis has been observed in 22 months after the surgery. Case 2: A 72-year old male presented with a 1.5×1.5 cm, dome-shaped nodule on his parietal region. A biopsy specimen revealed angiosarcoma. An additional mass manifested in the left temporal region within two weeks and was diagnosed as a skin metastasis of angiosarcoma by histopathology. Both masses were removed as one. Paclitaxel 60 mg/m2 was administered 12 times at six day intervals concurrent with radiation. He showed no side effects. No recurrence or metastasis has been observed in the 12 months after the surgery. We suggest that multimodal therapy, including paclitaxel, is an effective treatment for angiosarcoma, because the 2 cases mentioned above showed no recurrence or metastasis for at least 12 months.
In 1991, a 47-year-old male noted a mass in his left lumbar area; untreated, the mass gradually increased in size. About eight years later, a biopsy was performed at a nearby hospital. The patient was suspected of suffering from dermatofibrosarcoma protuberans (DFSP) and was subsequently referred to and hospitalized in our department. Histopathological analysis of the excised tumor confirmed DFSP-FS, which was associated with fibrosarcomatous (FS) lesions in certain regions. Since this operation, the patient has received regular follow-up. About two years after the operation, CT imaging showed a 2-cm nodular shadow in the S5 region of the left lung. Since a malignant tumor was suspected following biopsy, the left superior lobe was excised. The histological image of the lesion proved very similar to that of the FS components of the DFSP noted in the lumbar area. Hence, because distant metastasis occurs in DFSP-FS more commonly than with usual DFSP, stringent follow-up is required.
A 68-year-old man consulted us on 13 March, 1997, because his ala nasi has been deformed for one week. He had had erythema and vesicles, possibly herpes zoster, on the left cheek and nose on 17 February, which changed to erosion and then epithelized after ten days. On examination, he showed infiltrated erythema with hypoesthesia on the left cheek and nose. The deformation of the left ala nasi was also noticed, resulting in marked stenosis of the vestibule of the nose. Histological examination of the erythema revealed a palisading granuloma in the dermis and granulomatous vasculitis in the deep dermis and subcutaneous tissue. Varicellazoster-virus DNA was detected in the skin by polymerase-chain reaction. The patient was successfully treated with systemic administration of steroid Forty-seven cases reported previously were reviewed.
Recently in Japan, misunderstandings about the pathogenesis of atopic dermatitis (AD) and the strategies for the treatment of this disease, especially about the use of topical steroid, have led to a rapid increase of severe cases of AD caused by inadequate treatment. This prompted us to establish and distribute standard guidelines for AD therapy. In this guideline, the necessity of dermatological training to examine severe cases of AD is emphasized. It is stated that the present standard therapies for AD consist of the use of topical steroid and tacrolimus ointment (only for adult patients) for inflammation and emollient for dry and barrier—disrupted skin as the first line of attack, anti-histamines and anti-allergic drugs for pruritus, avoidance of apparent exacerbating factors, psychological counselling, and advice about daily life. The importance of correct selection of topical steroid according to the severity of the lesion is emphasized.