Intramedullary and retroperitoneal melanocytic tumor associated with congenital blue nevus and nevus flammeus: an uncommon combination of neurocutaneous melanosis and phacomatosis pigmentovascularis--case report.

Neurocutaneous melanosis (NCM) is a rare condition characterized by central nervous system melanocytic tumors associated with congenital melanocytic nevi. Phacomatosis pigmentovascularis (PPV) is an association of vascular nevus with pigmentary nevus. Aberrant maturation of neural crest-derived cells is considered to be related to pathogenesis in both conditions. However, association of NCM and PPV has not been reported to the best of our knowledge. Melanocytoma, which usually involves the leptomeninges or spinal cord, is extremely rare in the retroperitoneum. We present here a case of a patient with NCM, PPV, and melanocytic tumors in the spinal cord and retroperitoneum, which were treated surgically. A 40-year-old woman had a 2-year history of dysesthesia and weakness in the left leg. History included congenital giant blue nevus-like lesion in the trunk, a port-wine stain in the sacral area, and Caesarean section performed 8 years before, when diffuse pigmentation in the peritoneum was noted. Magnetic resonance (MR) imaging of the spine revealed an intramedullary tumor at T10 level with paramagnetic signal characteristics. The spinal cord tumor was totally removed, and the histological diagnosis was melanocytoma. Three months later, a left retroperitoneal mass with histological features of melanocytic tumor was removed. Neither tumors recurred and the patient stays ambulatory 4 years after the surgery. Multiple subtypes of melanocytic tumors with distinctive features of NCM and PPV can develop simultaneously, mimicking malignant melanoma. Gross total resection of each tumor, when indicated, is beneficial.

Lupus miliaris disseminatus faciei successfully treated with tranilast: report of two cases.

We report two cases of lupus miliaris disseminatus faciei (LMDF) in which oral tranilast was effective. In case 1, the patient was a 33-year-old woman who had developed pale red papules on her face, especially around her eyes and lower jaw, approximately 7 months previously. Examination of a skin biopsy specimen revealed epithelioid cell granulomas accompanied by caseous necrosis, and a diagnosis of LMDF was made. The patient was treated successively with azithromycin, roxithromycin and minocycline hydrochloride, but there was no improvement. When we tried oral tranilast therapy, flattening of the papules was observed 2 weeks after the start of treatment, and by 1 month the papules had almost disappeared. In case 2, the patient was a 39-year-old man who had broken out in erythematous papules on both upper and lower eyelids, with some accompanied by scaling, 2 years before the initial examination. Pathological specimen revealed epithelioid cell granulomas accompanied by caseous necrosis, and a diagnosis of LMDF was made. There was no improvement when treated orally with minocycline hydrochloride or doxycycline hydrochloride, and treatment was switched to oral tranilast therapy. After 1 month of treatment, the papules had almost disappeared. We concluded that oral tranilast therapy should be tried as a treatment for intractable LMDF.

A novel point mutation at donor splice-site in intron 42 of type III collagen gene resulting in the inclusion of 30 nucleotides into the mature mRNA in a case of vascular type of Ehlers-Danlos syndrome.

Vascular type of Ehlers-Danlos syndrome (EDS) is the most severe type of EDS. It is an autosomal dominantly inherited disorder that results from mutations within the alpha1 type III collagen gene (COL3A1). We report a novel point mutation at donor splice-site in intron 42 of type III collagen gene resulting in the inclusion of 30 nucleotides into the mature mRNA in a case of vascular type of EDS. Since the age of approximately 8 months, the patient had had repeated episodes of purpura and gradually developed thin, translucent skin. She had a past history of pneumothorax. At the initial examination, she was found to have the characteristic facies, i.e., bird-like face, of the vascular type of EDS, thinning of skin over the limbs and trunk, and scattered purpura. The blood vessels under the skin could be clearly visualized. She showed hypermobility of the small joints of all the four limbs and acrogeric changes of the hands and feet. Analysis of the amount of collagen synthesized from cultured dermal fibroblasts by SDS-polyacrylamide gel electrophoresis and fluorography was conducted based on the clinical suspicion of the vascular type of EDS, and a marked reduction in the synthesis of type III collagen was observed. Genetic analysis of the COL3A1 revealed a novel point mutation at the donor splice-site of intron 42, which resulted in the inclusion of 30 nucleotides into the mature mRNA of one allele.

Effect of erythromycin A and its new derivative EM201 on type I collagen production by cultured dermal fibroblasts.

Thinning of the dermis is the principal histological change in atrophic skin disorders and aged skin. It is caused due to a decreased amount of collagen in the dermis. Macrolides have been reported to exert various pharmacological activities, including anti-inflammatory activity, tumor angiogenesis inhibition and growth inhibition of fibroblasts, in addition to antimicrobial activity. In this study, we investigated the effects of erythromycin A (EMA) and its new derivative EM201 on type I collagen production by cultured dermal fibroblasts. Dermal fibroblasts were cultured with 10(-9) M-10(-5) M EMA or EM201, and collagen production was measured by incubation with radioactive proline, SDS-polyacrylamide gel electrophoresis and fluorography. mRNA levels were measured by Northern blots analysis, and to investigate transcriptional levels luciferase assays were also performed. The results showed that both EMA and EM201 increased collagen production and type I collagen mRNA level (to a maximum of 200% with EMA and 250% with EM201) in a dose-dependent manner in cultured dermal fibroblasts. Transcription of the type I collagen gene was also increased by both macrolides. These results suggest that EMA and EM201 have the potential to improve the thinning of the dermis in atrophic skin disorders and aged skin.

Effects of UVA irradiation following treatment with 8-methoxypsoralen on type I and type III collagen synthesis in normal and scleroderma fibroblast cultures.

Recent studies have demonstrated the efficacy of PUVA (psoralen plus ultraviolet A irradiation) therapy against sclerotic skin lesions in scleroderma, although the mechanisms underlying the improvement of the skin sclerosis by this therapy remain unknown. We investigated the effects of ultraviolet A (UVA) irradiation following the treatment with 8-methoxypsoralen on types I and III collagen synthesis and the gene expression of collagenase in cultured normal and scleroderma fibroblasts. The treatment reduced types I and III collagen synthesis and consequently, the types I and III collagen mRNA levels, in a UVA dose-dependent manner in both the normal and SSc fibroblasts, whereas the mRNA levels of collagenase remained almost unaltered. These results suggest that reduction of collagen synthesis by the fibroblasts may be one of the mechanisms underlying the efficacy of PUVA therapy against the sclerotic skin lesions in scleroderma.

Discoid lupus erythematosus exacerbated by contact dermatitis caused by use of squaric acid dibutylester for topical immunotherapy in a patient with alopecia areata.

A 57-year-old Japanese male patient with an 18-year history of discoid lupus erythematosus (DLE) presented with alopecia on his scalp, and was clinically diagnosed to have alopecia areata. He was started on topical immunotherapy with squaric acid dibutylester (SADBE) for the treatment of alopecia areata. The patient was first sensitized with the application of 2% SADBE on the right upper arm, followed subsequently by re-exposure to a low concentration of SADBE to provoke contact dermatitis on the scalp as treatment. Approximately 2 months later, he developed multiple red scaly lesions on his scalp and face, which were diagnosed histopathologically as DLE. DLE is known to be exacerbated by a variety of factors, including sunlight, X-rays, tattoos, burns, and some forms of cutaneous trauma, including dermatitis. However, to the best of our knowledge, there have only been two reported cases of DLE exacerbated by contact dermatitis.

EM703, the new derivative of erythromycin, inhibits transcription of type I collagen in normal and scleroderma fibroblasts.

BACKGROUND: Excessive accumulation of collagen in the skin and internal organs in systemic sclerosis (SSc) is considered to result from enhanced transcription of collagen in fibroblasts. Macrolides have been reported to show various pharmacological activities. Recently, it was reported that EM703, a new derivative of erythromycin, improved bleomycin-induced pulmonary fibrosis in mice. OBJECTIVE: Therefore, we attempted to examine the effects of EM703 on the type I collagen synthetic activity in normal and SSc dermal fibroblasts. METHODS: Normal and SSc dermal fibroblasts were cultured with various concentrations of Erythromycin A or EM703 for 48h. Amount of type I collagen in the culture medium was measured with ELISA with anti-type I collagen antibody. Type I collagen mRNA levels were measured by northern blots analysis and type I collagen transcription and regulation of the human COL1A1 promoter activity were examined by transient transfection and luciferase assay. Electrophoretic gel mobility shift assay was also performed for measurement of binding activities of DNA binding factors to the COL1A1 promoter. RESULTS: We found that EM703 reduced collagen production and the mRNA levels of alpha1(I) collagen in a dose-dependent manner in the normal fibroblasts. The transcription of COL1A1 was downregulated as detected by the luciferase assay. The downregulation was also detected using DNA containing various short lengths of the COL1A1 promoter region. EM703 did not inhibit COL1A1 transcription when the luciferase assay was performed using DNA containing the COL1A1 promoter with a short substitution mutation of the CCAAT box. Decreased production of type I collagen at the transcriptional level was also found in SSc fibroblasts treated with EM703. CONCLUSION: These results suggest that EM703 inhibits the transcription of type I collagen in both normal and SSc fibroblasts, and that the transcription is inhibited through the CCAAT box of the COL1A1 promoter.

Syringocystadenoma papilliferum associated with apocrine poroma.

A 65-year-old Japanese man presented with a gradually enlarging mass on the right side of the abdomen, which he had first noticed about 4 years previously. He was otherwise asymptomatic. Histopathological examination of the mass revealed an aggregation of neoplastic cells (tumor cell nests) with cellular proliferation extending from the epidermis to the dermis. The tumor consisted of two histologically distinct parts. One part was composed of uniformly small cells with a cuboidal appearance. Some ductal structures were visualized, and some of the cells lining the ductal lumina contained decapitation secretions. These histological changes were consistent with the diagnosis of apocrine poroma. The remaining part of the tumor was composed of cystic invaginations with numerous projections oriented toward the lumen. There were two rows of cells in the projections; the cells on the luminal side were columnar, and those at the apical aspect were small cuboidal cells. These histological changes were characteristic of syringocystadenoma papilliferum (SCAP). Based on these findings, a diagnosis of SCAP associated with apocrine poroma was made. To the best of our knowledge, there have been no previous reports of such a case in the published work.

Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin.

Human papilloma virus (HPV) is known to be an etiologic agent for benign warts of the skin. Recently, HPV have been detected in malignant skin and mucosal diseases suggesting that HPV infection can induce malignant skin tumors. In the present study, we examined the presence of mucosal HPV DNA in normal tissue, Bowen's disease (BD), Bowenoid papulosis (BP) and squamous cell carcinoma (SCC) of the skin. We detected the HPV DNA with polymerase chain reactions, and identified the type by DNA sequencing. In the results, we detected HPV DNA in none of the 17 normal controls, two of the three BP (66.7%), one of the 21 BD (4.8%), and six of the 26 SCC of the skin samples (23.0%). The occurrence rates of HPV in BP and SCC were significantly elevated compared to that of normal controls (P < 0.01 and P < 0.01, respectively). In addition, the occurrence rate of HPV in BP was significantly elevated compared to that of BD (P < 0.05). The reproducibility was confirmed with a polymerase chain reaction (PCR) with another primer pair. Of the two cases of BP with positive HPV DNA, one case showed HPV 31 and the other case HPV 16. The case of BD with positive HPV DNA showed HPV 31. Of the six cases of SCC with positive HPV DNA, one case showed HPV 16, another case HPV 34, and the other four cases HPV 31. These results showed that mucosal HPV, including HPV 31 and 16, could be detected in SSC of the skin. Mucosal HPV, not only the epidermodysplasia verruciformis type, appear to induce malignant skin tumors.