Shoko Arakawa

Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis

Atopic dermatitis is characterized by Th2‐dominant immunity. Recently many intracellular molecules have been reported to regulate cytokine expression and T cell differentiation. GATA‐3 and T‐box expressed in T cells (T‐bet) are transcription factors that play a critical role in the development of Th2 and Th1 immunity, respectively. Suppressor of cytokine signalling (SOCS)‐3 and SOCS‐5, are negative regulators of the cytokine signalling induced by IL‐12 and IL‐4, respectively. Txk is a transcription factor that activates IFN‐γ gene directly. The present study was designed to identify intracellular molecules that are responsible for the pathogenesis and the imbalance of cytokines in atopic dermatitis. Semi‐quantitative RT‐PCR revealed that in peripheral blood mononuclear cells without any stimulation the levels of mRNA for GATA‐3 and SOCS‐3 were elevated, the levels of mRNA for Txk were depressed and the levels of mRNA for T‐bet and SOCS‐5 were comparable in patients with atopic dermatitis as compared with healthy controls. In addition, successful therapy normalized levels of mRNA for GATA‐3 and Txk, although those for the others including IL‐4, IL‐5, IL‐10, IL‐13 and IFN‐γ did not change. Levels of Txk mRNA correlated with those of IFN‐γ, while the mRNA levels of the other regulators did not correlate with those of any of the cytokines. These results suggest GATA‐3 and Txk might be involved in skin lesions, while SOCS‐3 might be associated with an imbalance of cytokines that is difficult to normalize in atopic dermatitis.

In vivo levels of IL-4, IL-10, TGF-β1 and IFN-γ mRNA of the peripheral blood mononuclear cells in patients with alopecia areata in comparison to those in patients with atopic dermatitis

Alopecia areata (AA) has been considered to be supported by an aberrant expression of IFN-γ as a result of antigen dependent immune response. On the other hand, AA sometimes concurs with atopic diseases, although the mechanism of the concurrence is not clear. This study was designed to elucidate the immune status of AA and the similarity between AA and atopic dermatitis (AD) by analysis of in vivo levels of mRNA of Th1, Th2, and suppressive cytokines of peripheral blood mononuclear cells (PBMC). Using semiquantitative RT-PCR, the levels of cytokine mRNA were measured in freshly isolated PBMC of 47 patients with AA, 15 patients with AD, and 12 healthy controls (HC). The levels of IL-4, IFN-γ, and TGF-β1 mRNA were lower in patients with AA than those in HC. The levels of IL-10 mRNA in AA were comparable with those in HC. Decreased levels of IFN–γ and TGF-β1 were also shown in patients with AD. These results indicated a similarity (decreased levels of IFN-γ and TGF-β1) between AD and AA based on the cytokine profile. In addition, decreased levels of IL-4 mRNA in AA might also explain the experience that the severity of atopic disease coincident with AA is mild in the most of cases. Next, we compared the levels of these cytokine mRNA among the three subgroups of AA that were categorized based on the severity of the symptoms: mild, severe and totalis. Although there was no significant difference between any combinations of the subgroups, there was a tendency to increase the levels of IFN-γ mRNA and to decrease the levels of IL-4 mRNA according to the severity of alopecia. However, the levels of IFN-γ mRNA in any subgroups were less than those of HC. These results suggest that IFN-γ is therefore involved in the pathogenesis of AA, although the information from PBMC is limited. In conclusion, AA might be induced by an aberrant expression of IFN-γ in individuals whose PBMC produce low amounts of IFN-γ and TGF-β1. Further analysis is therefore required to investigate the phenotypes of the population in PBMC with or without reference to regulatory T cells.

Hidroacanthoma simplex: a case report and analysis of 70 Japanese cases.

Hidroacanthoma simplex (HS) is a rare benign eccrine adnexal tumor, which is often clinically misdiagnosed as seborrheic keratosis, Bowen’s disease or other adnexal tumors [1]. Here we report a case of HS that had been treated as chronic dermatitis for some years, and we analyze a total of 70 Japanese cases of HS. A 73-year-old woman presented with a 15-year history of a gradually growing cutaneous lesion on her left lower leg. The lesion had been treated with topical ointments under the diagnosis of chronic dermatitis for some years at another dermatologic clinic. At that visit the lesion was a well-defined, brownish but irregularly colored plain plaque with a few papules, measuring 20 ! 40 mm (fig. 1). A biopsy specimen was taken from the lesion under a diagnosis of Bowen’s disease. Histological examination revealed well-circumscribed intraepidermal nests of clear-looking basaloid cells (fig. 2a, b). A few small ductal structures and no clumping cells were observed. In an immunohistochemical study, epithelial membrane antigen and S100 protein were both negative, and keratin (polyclonal rabbit antihuman cytokeratin; Dako) and carcinoembryonic antigen were partially positive. We diagnosed this tumor as HS. Although a wide excision was recommended, our patient refused an operation. The patient has been carefully examined periodically. Hidroacanthoma simplex was first described by Smith and Coburn in 1956 [2]. The tumor is expressed as intraepidermal poroma, since nests of tumor cells are seen within the normal epidermal cells [3]. We counted a total of 69 Japanese cases appearing in the Japanese literature between 1983 and 2003. Among 70 cases, including ours, 19 occurred in men and 47 in women (4 cases were not described). The male-to-female ratio was 1:2.5. HS seemed to occur more often in females than in males. This differs from the previous report, which suggested there was no sex predilection in HS [1]. Ages ranged from 24 to 91 years in our study, with an average age of 65.8 years, and 80% of the patients were more than 50 years old. In the present study, HS occurred more often on the trunk (back 10, thorax 4, abdomen 6, buttock 10; 42.8%) and the lower extremities (thigh 16, lower leg 11, foot 5; 45.7%) than on the head and neck (2 cases; 2.9%) or the upper extremities (2 cases; 2.9%). Both the trunk and lower extremities seemed to be predilection sites. This result also differs from the previous report, which suggested that the limbs were more likely to be involved than the trunk or head [1]. The tumors varied in size from 4 ! 7 mm to 80 ! 90 mm, and they were colored light red, dark red, brown or dark brown. Their clinical appearance was reported as verrucous plaque, plain plaque, an aggregation of papules or a mixture of these. Most lesions were clinically diagnosed as seborrheic keratosis, Bowen’s disease, basal cell carcinoma or other adnexal tumors. No cases were diagnosed as HS clinically. It seems difficult to make a diagnosis of HS clinically, and this is suggestive of the existence of some other cases of HS that have been treated insufficiently like our case.

Three cases of 'mechanic's hands' associated with interstitial pneumonia: possible involvement with foot lesions.

We describe three cases of the rare combination of lateral erythema and hyperkeratosis of the fingers that typify a condition known as ‘Mechanics Hands’. The first and the third cases were unusual in that the condition was associated with cutaneous involvement of the feet and interstitial pneumonia but not with myositis, or with only mild muscular involvement, while the second case was typical, being accompanied by myositis and detectable antibodies against histidyl transferase. We propose that Mechanics Hands can occur in association with foot lesions and interstitial pneumonia, even if it is not accompanied by myositis.

Fexofenadine, an H1-receptor antagonist, partially but rapidly inhibits the itch of contact dermatitis induced by diphenylcyclopropenone in patients with alopecia areata.

Antihistamines have been used for the treatment of not only allergic diseases such as allergic urticaria and rhinitis, but also of eczematous skin diseases because of their anti‐pruritic effects. Moreover, the pruritus associated with eczematous diseases is considered to be induced, in part, by histamine. However, it is unclear whether antihistamines inhibit the itch of eczematous diseases in the absence of topical corticosteroids. In this study, we investigated the anti‐pruritic effect of the antihistamine, fexofenadine, on the itch of contact dermatitis that was induced by topical application of diphenylcyclopropenone for the treatment for alopecia areata. Thirteen patients with alopecia areata, who had been treated weekly with topical immunotherapy with diphenylcyclopropenone for 3 months to 2 years, recorded the severity of their itching on a visual analog scale before and 3, 6, 12, 24, 48 and 72 h after application of diphenylcyclopropenone for 4 consecutive weeks. Seven patients took fexofenadine during the first and third weeks, and six patients took fexofenadine during the second and fourth weeks. The severity of itching reached a maximum 6–12 h after the induction of the contact dermatitis in most of the patients. However, fexofenadine partially but rapidly reduced the severity of itching for 72 h during the entire period of treatment in the absence of topical corticosteroids. Our results suggest that fexofenadine can be beneficial in the daily management of patients with itching due to eczematous disease.

Analysis of 256 cases of basal cell carcinoma after either one‐step or two‐step surgery in a Japanese institution

Basal cell carcinoma (BCC) is a common skin cancer that arises from the cells of the basal layer of the epithelium or from the external root sheath of the hair follicle. In the present report, 256 cases treated surgically between 1999 and 2008 in our department were retrospectively analyzed. The most frequent BCC locations included the face (77.8%), especially the nose (26.9%) and eyelids (21.5%). Incomplete excisions occurred in 21 cases. Two patients experienced local recurrence; one of these patients exhibited a bone metastasis while the other had a metastasis of the parotid gland without the local recurrence. The rate of local BCC recurrence was 0.78%, which is lower than that described in previous reports. We categorized BCC into four histological types: superficial, solid, adenoid and infiltrative. The solid type was the most frequent histological type (62.1%). For preventive recurrence, we treated BCC patients with two‐step surgery when the tumor was large or histologically invasive. At the first step, we excised the tumor with a sufficient safety margin, and at the second step, we performed reconstruction after the histological confirmation that no remnant malignant cells were in the tumor margins. In the present report, no local recurrence occurred in patients following the two‐step surgery. Therefore, two‐step surgery is recommended for tumors at locations and with histological types related to frequent recurrence.

Skin Cancer Screening on a Fishing Island and in an Inland Agricultural Area of Japan

We performed skin cancer screening from 2000 to 2004 at two locations in Japans Oita Prefecture: Himeshima, a small fishing island, and Naoiri, an inland agricultural area. We found 108 and 21 cases of AK in Himeshima and Naoiri, respectively. None of the AKs transformed into SCC, and 21.7% of the AKs underwent spontaneous remission during our observation period. The prevalence and incidence of AK in Himeshima were five times higher than in Naoiri: 1,399 and 826 per 100,000 population, respectively, in the fishing village, vs. 261 and 164 in the agricultural community. Seven and three cases of BCC were observed in Himeshima and Naoiri, respectively. There were two cases of SCC in Himeshima. The highest risk ratio of skin types I to III was 9.2 in Himeshima. Although people engaged in outdoor occupations are thought to be more prone to skin cancer and precancerous skin lesions, our results suggested different potentials for AK in people engaged in different outdoor occupations.