Soji Yamazaki

Quantitative analysis of microchimerism in systemic sclerosis skin tissue

Abstract It has been reported that more male DNA of presumed fetal origin is present in the blood and skin of women with systemic sclerosis (SSc) as compared with healthy controls after delivery, but these findings are controversial. We sought to determine whether male cell DNA is present in SSc using a quantitative polymerase chain reaction for Y chromosome DNA. The study groups comprised 57 healthy women, 49 patients with SSc and 30 patients with connective tissue diseases other than SSc who had given birth to at least one son and/or had experienced fetal loss. The intensity of the PCR bands on negatives of gel photographs was quantified with a video densitometer linked to a computer analysis system. Positive Y chromosome DNA was found in 20 healthy women, 14 SSc patients and 6 patients with connective tissue diseases other than SSc. The occurrence rate of DNA equivalents of male cells among the three groups showed no significant differences. The number of male cell DNA equivalents per 80 ng tissue DNA in SSc patients (4.59 ± 9.63), however, was significantly higher than in healthy women (1.83 ± 4.96; P < 0.05) and in patients with connective tissue diseases other than SSc (0.27 ± 0.64; P < 0.01). The occurrence rate of fetal loss in male cell DNA-positive SSc (eight) was significantly higher than in male cell DNA-negative SSc patients (four; P < 0.01). No correlation was found between the number of male cell DNA equivalents and birth of sons or clinicolaboratory findings. These results indicate that the elevated amount of male cell DNA in SSc skin tissue may contribute to the pathogenesis of SSc.

The polymorphism of transforming growth factor‐β1 gene in Japanese patients with systemic sclerosis

Background Transforming growth factor (TGF)‐β has been shown to be a potent stimulator of collagen production by fibroblasts, and could play a role in the pathogenesis of systemic sclerosis (SSc).

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, Bowens 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.

Cutaneous localization of endothelin-1 in patients with systemic sclerosis: immunoelectron microscopic study

Background Endothelin‐1 (ET‐1) has some relation to the pathogenesis of systemic sclerosis (SSc) and Raynauds phenomenon. This study was performed to determine the localization of ET‐1 in patients with SSc.

Quantitative echographic analysis of photochemotherapy on systemic sclerosis skin

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, in which development of fibrosis, vascular insufficiency and inflammatory processes are prominent in the skin as well as in other organs. We studied the effect of photochemotherapy with quantitative echography in SSc. Dermal echo intensity and dermal thickness was measured using high-frequency dermal echography before and after therapy. The dermal echo intensity after photochemotherapy (33.51±9.34) significantly increased than that before therapy (21.23±6.00) (P<0.01), while dermal thickness (1.20±0.20) significantly decreased than that before therapy (1.38±0.18) (P<0.05). Photochemotherapy was more likely to improve dermal edema, not fibrosis, because echo intensity after treatment was significantly elevated with that before treatment in patients with edema. Quantitative echographic analysis was concluded to be a reliable method in evaluating the change of skin edema in SSc.

Digital ulcers and necroses: novel manifestations of angiocentric lymphoma.

We describe a patient with angiocentric lymphoma whose presenting features were multiple areas of digital ulceration and necrosis, including deep ulcers on both great toes. He lacked the lateral halves of both earlobes because of multiple ulcers. Skin biopsy revealed a patchy and diffuse infiltrate of lymphoid cells with nuclear atypia in the dermis and subcutaneous tissue. Angiocentric and angiodestructive features of the lymphoid cells, a prominent histiocytic infiltrate and some epithelioid cell granulomas were found. The results of immunohistochemical staining showed a T‐cell phenotype, and showed positive staining for apoptosis. He died in July 1999. Peripheral vascular disturbances including Raynaud’s phenomenon, digital skin ulcers and necroses are novel clinical symptoms in patients with angiocentric lymphoma, which should be added to the differential diagnosis in patients with peripheral vascular disturbances.

Electron-microscopic study of sclerodermatous chronic graft-versus-host disease

Background. Sclerodermatous chronic graft‐versus‐host disease (SC‐GVHD) resembles systemic scleroderma (SSD) closely, both clinically and histologically. Our purpose was to try to define the morphologic differences of collagen fibers between SC‐GVHD and SSD.

Successful treatment of granulomatous cheilitis with roxithromycin

Dear Editor, A 13-year-old boy visited our department on 14 May 2005 with the chief complaint of swelling of the lower lip, which had begun to develop approximately 1.5 years previously in the absence of any particular provoking factors. Initial clinical examination showed swelling of the entire lip area, including the lower lip (Fig. 1a). The patient had no subjective symptoms, including itching, and no evidence of facial nerve paralysis or a lingua plicata was recognized. A plain chest roentgenogram taken during a routine school health examination revealed no abnormalities. Although he had a past history of dental treatment, no carious teeth were recognized at the initial examination, and no metal crown had been used in the dental treatment. Laboratory examination revealed no hematological or biochemical abnormalities. The serum level of immunoglobulin E, which seemed to be associated with allergic rhinitis, was elevated to 1490 mg/dL. Histopathological findings in biopsy specimens of the swollen lips showed partial thickening of the epithelium, edema and vasodilation in the upper layer of the dermis. Infiltration by small round cells and granulomatous lesions were recognized in the middle and lower layers of the dermis (Fig. 2). Therefore, a diagnosis was made of granulomatous cheilitis. On 14 June 2006, the patient was started on oral minocycline at a dose of 100 mg/day, and the drug was continued for 45 days. Because no change in the condition of the lips was noted, oral azithromycin was begun at a dose of 1500 mg/week and administrated for another 10 weeks, however, the patient’s condition remained unresponsive to treatment. Subsequently, the patient was started on oral roxithromycin at a dose of 150 mg/day; with this treatment, the swollen lips began to improve gradually by 2 months after the drug was started, and subsided almost completely by 5 months after the start of the treatment (Fig. 1b). At present, approximately 6 months after the discontinuation of roxithromycin, there has been no relapse.

A Case of Angiolymphoid Hyperplasia with Eosinophilia (ALHE) of the Upper Lip

Angiolymphoid hyperplasia with eosinophilia (ALHE) is clinically characterized by intradermal or subcutaneous papules and/or nodules usually occurring in young adults. Lesions in the oral mucosa are extremely rare. We report a case and review the literature of ALHE cases involving the oral mucosa. A 40‐year‐old man presented with a painless, 20 × 20 mm, submucosal nodule on the upper lip. Histological examination of lip biopsy specimens revealed an increase in many small vessels. The vascular walls consisted of prominent endothelial cells with a histiocytoid appearance, which protruded into the lumen. Many eosinophils and lymphocytes were also seen around the vessels. The diagnosis of ALHE was made from the above findings.

A Case of Lichen Myxedematosus with Clearly Exacerbated Skin Eruptions after UVB Irradiation

We report a 48‐year‐old male with typical lichen myxedematosus, liver dysfunction, and diabetes mellitus. His skin eruptions were clearly exacerbated after accidental over‐irradiation by UVB. These findings were clinically and histologically confirmed. The pathogenesis is still unknown, but we consider it to be due to Koebner phenomenon.