Search

Summary A 54-year-old Japanese man without apparent immunosuppression presented with nodules with purulent drainage on the right lower leg. He had ringworm of the right leg and tinea unguium. A biopsy specimen of the nodule showed intradermal abscesses with fungal elements, and Trichophyton rubrum was cultured from both the pus and the biopsy specimen. Treatment with oral terbinafine resolved the nodules. Dermatophyte abscess is a rare, deep and invasive dermatophytosis, which is often associated with immunocompromised conditions. We provide a review of the literature including Japanese cases.

Background The recommended duration of antibiotic therapy for patients hospitalized with cellulitis is 5–14 days. However, factors that affect the duration of treatment have rarely been examined. Methods We conducted an observation study in a regional hospital in Japan to examine factors that affect the duration of antibiotic therapy for cellulitis. Our study included 102 patients with cellulitis of the lower extremities who were treated with intravenous cefazolin alone. Intravenous cefazolin was terminated when redness, swelling, and tenderness of the lower extremities disappeared, and subsequently the patients were discharged. The relationship between the duration (days) of treatment with intravenous cefazolin (DIVC) and clinical factors were analyzed. Results The median DIVC was 8 days (interquartile range, 7–10 days). On univariate analysis, DIVC correlated significantly with patient age (P = 0.0071) and with C-reactive protein levels before treatment (P = 0.0053). DIVC in patients with diabetes mellitus was significantly longer than that in patients without diabetes mellitus (P = 0.0033). DIVC in patients with blood stream infection was significantly longer than that in patients without blood stream infection (P = 0.029). On multivariate analysis, variables independently associated with longer DIVC included patient age (P = 0.044), C-reactive protein levels before treatment (P = 0.017), presence of diabetes mellitus (P = 0.0021), and presence of blood stream infection (P = 0.028). Conclusions Duration of treatment with intravenous antibiotics for cellulitis is associated with patient age, C-reactive protein levels, coexisting diabetes mellitus, and coexisting blood stream infection. These findings should be considered when treatment plans for cellulitis are devised.

A 75-year-old Japanese man presented with pruritic blisters and macules on his trunk and extremities. He had been on hemodialysis for 4 years because of chronic renal failure, and in recent months, a polymethylmethacrylate membrane had been used for dialysis. After a change in dialysis membrane to a cellulose triacetate membrane, pruritic tense blisters developed on the extremities in combination with marked blood eosinophilia. Physical examination showed erythematous macules and tense blisters on the trunk and extremities. A biopsy specimen of an erythematous macule showed subepidermal vesicles and eosinophils that attached to the dermal-epidermal junction. Serum level of eosinophilic cationic protein was elevated. From clinical, histological, and immunological findings, a diagnosis of bullous pemphigoid was made. New blisters continued to erupt during the period in which the patient used the cellulose triacetate membrane dialyzer, and even after the use of clobetasol propionate. It resolved only after the patient came back to the use of a synthetic membrane dialyzer. We discontinued the use of clobetasol propionate, and neither bullous eruptions nor blood eosinophilia recurred. These observations suggest that cellulose membrane may be involved in the development of bullous pemphigoid through activation of eosinophils in the blood and the skin lesion, as in the present case.

A 5-year-old Japanese girl presented with a 4-month history of a solid dermal tumor on the left side of her forehead. She had neither diathesis for autoimmune disorders nor family history of alopecia areata. Her left eyebrow and vellus hairs around the tumor had been lost as the tumor grew. Examination revealed a 1 cm, bluish, solid, dermal tumor surrounded by a 5-cm diameter alopecia, where the left eyebrow and the vellus hairs on the forehead were missing (figure 1A). A presumptive clinical diagnosis [...]

Bullous pemphigoid is an autoimmune blistering skin disease of the elderly that may be preceded by a pruritic, urticarial or eczematous eruption. We report a case of bullous pemphigoid preceded by prodromal eczematous eruptions that lasted an unusually long time of 11 years. Elderly patients with persistent pruritic or eczematous eruption of unknown etiology should be carefully followed, as bullous pemphigoid may be a potential diagnosis.

金沢大学医学部附属病院皮膚科, Objective: Our purpose was to determine the serum levels and frequency of antiphospholipid antibodies (aPLs) and confirm the clinical importance of these antibodies in patients with autoimmune blistering disease (ABD). Methods: IgG and IgM anticardiolipin antibodies (aCL), IgG anticardiolipin-β2 glycoprotein I complex antibody (aCL/β2GPI), and IgG antiphosphatidylserine-prothrombin complex antibody (aPS/PT) were examined with an enzyme-linked immunosorbent assay in 71 patients with ABD, including pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid. Results: The prevalence of IgG aCL, IgM aCL, aCL/β2GPI, and IgG aPS/PT was positive for 22.4%, 9.1%, 9.9%, and 25.4% of the ABD patients, respectively, whereas these antibodies were not detected in any of the normal control subjects. Ten of 20 patients with ABD who were attending our hospital in 2004 tested positive for aPLs, and thromboembolism was detected in 7 of 10 patients with aPLs. Limitations: Follow-up studies, especially with a large patient group, will be needed to clarify the clinical relevance of aPLs in ABD. Conclusion: aPLs are frequently detected in patients with ABD. Careful examination and follow-up for thromboembolism may be necessary in ABD patients with aPLs. © 2007 American Academy of Dermatology, Inc.

A 70-year-old Japanese man presented with a 5-year history of refractory indolent onycholysis of the little finger of the right hand. Roentgenograms did not show involvement of the bone. Histological examination revealed an epithelial tumor consisting of lobular masses varying in size. The tumor was composed of keratinocytes varying in atypicality and showed infiltrative growth into the dermis but not into the phalangeal bone. The tumor had cystic structures composed of eosinophilic amorphous keratin and a surrounding thin layer of keratinocytes. Characteristically, the epithelium in the center of the tumor abruptly changed into amorphous keratin without the formation of intervening keratohyaline granules. From these findings, the mass was diagnosed as onycholemmal carcinoma. Immunohistochemically, the tumor showed a keratin profile comparable to that of the nail bed epithelium and a smaller number of Ki-67-positive proliferating tumor cells compared with those of a previous case of onycholemmal carcinoma.

緑膿菌による趾間感染症(Pseudomonas toe web infection)の2例を経験した。治療は“hyperkeratoticrim”と表面滲出物のdebridementおよび1％酢酸液による足浴が有効であった。緑膿菌はウッド灯を用いると緑色の蛍光を発するため趾間感染症の早期診断に有用で治療効果判定にも使用できた。趾間感染症は宿主側の感受性および環境要因により再発を繰り返しやすい。今回の症例では1％酢酸液足浴による局所管理が再発予防にも有用であった。

Biotin deficiency is rarely encountered in an infant on weaning from breast and formula feeding. It is characterized by alopecia and scaly, erythematous dermatitis distributed around the body orifices. We report a 5-month-old Japanese infant with typical skin lesions who had been diagnosed as a neonate with dyspepsia and fed only an amino acid formula. Serum and urine levels of biotin were below the normal range, but zinc and biotinidase were within normal range. Urinary excretion of 3-methylcrotonylglycine, 3-hydroxyisovaleric acid, and methylcitric acid was significantly elevated. Daily oral supplementation with 1 mg of biotin resulted in dramatic improvement of the periorificial dermatitis and hair growth together with a complete disappearance of the organic aciduria. Our case shows that the characteristic skin manifestations are the most important clue to the diagnosis of biotin deficiency and demonstrated that urinary excretion of biotin and organic aciduria, rather than the serum concentration of biotin, are the sensitive indicators for evaluating the patient's status of biotin deficiency.

73歳の男性。高血圧に起因する慢性腎不全があり9ヵ月前から血液透析を開始した。両手の指の難治性の潰瘍のため当科に入院した。手指の潰瘍は2ヵ月前から出現し，右手の方が左手より重症であった。下肢には虚血症状はなかった。入院時検査では血清クレアチニン値の上昇，高コレステロール血症，高リン血症，副甲状腺ホルモンの軽度増加が認められた。手の単純X線写真では橈骨動脈，尺骨動脈，および指の動脈に石灰化が認められた。動脈造影では右前腕の内シャントへ大量の血液が流入し，指の動脈への血流は低下していた。以上の臨床症状と検査所見から，動脈硬化，二次性副甲状腺機能亢進症，steal症候群の3者が指尖潰瘍の形成に関与したものと推測した。プロスタグランジンE1製剤の静注，リン吸収阻害剤や高脂血症治療薬などの内服，壊死組織の除去を含む局所処置により潰瘍は消失した。

症例は84歳女性。右下顎部に半球状に隆起する紅色腫瘤を認め, 病理組織では真皮上層から皮下脂肪織にかけて結節状に増殖する腫瘍細胞を認めた。腫瘍細胞は小型で細胞質に乏しくCK20染色陽性で, 電顕像にて細胞質辺縁に電子密度の高い顆粒 (dense core granule) を認めた。メルケル細胞癌と診断し, 放射線単独治療を施行した。6MeVの電子線にて総線量48Gyを照射したところ2ヵ月後には腫瘍は完全に消失した。その後明らかな再発・転移は認めていない。メルケル細胞癌は放射線感受性が高い腫瘍であり以前より放射線単独治療の有効性が指摘されている。本邦において放射線単独治療を施行された11例のメルケル細胞癌につき検討したところ, 6例に関しては観察期間中明らかな再発・転移を認めなかった。これら6症例には腫瘍長径が3センチ以下と比較的小型で, 初診時に所属リンパ節転移を認めていない, という共通した特徴があった。

患者は55歳の男性。10数年前に右足関節に顕著な腫脹と疼痛を経験し，その後下腿から足背にかけて色素沈着に気づいた。3年前より右外果の難治性潰瘍に苦しむようになり，他医にて遊離筋皮弁術を施行されたがその11ヵ月後に皮弁周囲に潰瘍が再発し当科を受診した。初診時，右外果と内果，皮弁周囲および足背に最大径10cmまでの底部が黄色を示す潰瘍を認めた。逆行性静脈造影で造影剤の膝下までの逆流を認め深部静脈弁機能不全症と診断した。静脈弁形成術後，右下腿・足部の潰瘍は速やかに縮小し約4ヵ月後に完全に上皮化した。自験例は，深部静脈弁機能不全を精査するためには逆行性静脈造影が有用であり，また深部静脈弁機能不全による難治性潰瘍において弁形成術が奏効することを示している。静脈性潰瘍における原因精査とその結果に基づいた適切な治療の重要性を強調したい。

Studies have suggested that psoriasis vulgaris is mediated by type 1 T cells. In this study, we examined both chemokine receptor expression and intracellular cytokine production by circulating T cells to check the type 1/type 2 balance in psoriasis. CCR4+ and CXCR3+ T cells predominantly produced interleukin-4 and interferon-γ, respectively. The frequency of interferon-γ-producing cells and that of CXCR3+ cells in circulating CD4+ T cells were similar for psoriatic patients and healthy control subjects. By contrast, the frequency of CCR4+CD8+ T cells and CCR4/CXCR3 ratio in circulating CD8+ T cells were significantly higher in psoriatic patients than in healthy control subjects. Analysis of intracellular cytokine production also indicated relative increase of type 2 CD8+ T (Tc2) cells in peripheral blood from psoriatic patients. The frequency of circulating Tc2 cells directly correlated with Psoriasis Area and Severity Index. Immunohistochemical analysis showed that not only CXCR3+CD8+ T cells but also a similar number of CCR4+CD8+ T cells infiltrated the psoriatic epidermis and dermis. Our findings suggest an increase in Tc2 cell number in blood from psoriatic patients, and the association of Tc2 cells with inflammation in psoriasis.

A 10-year-old Japanese girl presented with a rhomboid-shaped brown macule, 4 x 3 mm in size, on the sole of the right foot. Dermoscopic examination revealed a number of black dots and globules on the ridges of the skin, marking an area of symmetrical brown pigmentation. On the periphery, a streak-like arrangement of black dots/globules on the brown pigmentation was observed along the ridges, simulating a “starburst” pattern. The lesion was excised and histological examination showed a symmetrical wedge-shaped compound melanocytic lesion that consisted of junctional and intradermal nests of a mixture of large spindle and epithelioid cells. None of the cells were atypical, and maturation of the cells with increasing depth was observed. From these findings, a diagnosis of Spitz nevus was made. Transepidermal elimination of nevus cell nests was observed and there were small groups of degenerated melanin-laden cells in the cornified layer. Masson Fontana stain revealed fine melanin deposits in the nevus cells of the junctional and intradermal nests, as well as heavy melanin deposits in the small groups of degenerated cells in the cornified layer. The distribution of melanin may contribute to a unique dermoscopic finding in this case.

We describe a patient in whom pemphigus foliaceus developed after cutaneous squamous cell carcinoma (SCC) metastasized to regional lymph nodes. Immunologic analysis revealed that production of anti-desmoglein 1 autoantibodies started when SCC metastasized, and the SCC expressed desmoglein 1, suggesting a pathogenic role of metastasized SCC in developing pemphigus foliaceus. (J Am Acad Dermatol 2001;45:767-70.)

Background: Recent studies have reported that T H 1 and T H 2 cells express CXCR3 and CCR4, respectively. Objective: Our goal was to assess the association of CCR4 and CXCR3 expression with T H 2 and T H 1 cells and association of CCR4 and CXCR3 expression with inflammation in patients with atopic dermatitis (AD). Methods: Intracellular cytokine production and chemokine receptor expression in blood T cells were examined by flow cytometry. Immunohistochemical expression of chemokine receptors was also investigated in chronically lesional skin. Results: CCR4 + and CXCR3 + CD4 + T cells predominantly produced IL-4 and IFN-γ, respectively. Although the frequency of CXCR3 + cells among CD4 + CD45RO + T cells was similar for patients with AD (n = 29) and healthy control subjects (n = 19), patients with severe AD (n = 14) had a reduced frequency of CXCR3 + cells. In contrast, the frequency of CCR4 + cells and the CCR4/CXCR3 ratio were higher in patients with AD (n = 22) than healthy control subjects (n = 16) and correlated with disease severity of AD. The frequency of CCR4 + cells correlated positively with eosinophil numbers and serum IgE levels, whereas the frequency of CXCR3 + cells correlated inversely with eosinophil numbers. The frequency of CCR4 + or CXCR3 + cells was similar in patients with psoriasis (n = 6) and healthy control subjects. Immunohistochemical analysis showed that the frequency of CCR4 + cells among CD4 + T cells in chronically lesional skin of patients with AD (n = 9) was higher than that of patients with psoriasis (n = 4). Conclusion: Our data suggest the association of CCR4 expression with T H 2 cells, the predominance of CCR4 + cells in blood from patients with AD, and an important role of CCR4 in the migration of T H 2 cells from blood into AD lesional skin. (J Allergy Clin Immunol 2001;107:353-8.)

副腎皮質ホルモン剤内服に問題のあった水泡性類天泡瘡患者4名にテトラサイクリンとニコチン酸アミドの併用内服療法(TC/NA療法)を行い有効であった。症例1: 70歳女性。水痕性類天泡瘡に対するプレドニゾロン内服の減量時に再燃した。DDSやアザチオプリンの併用は無効で, TC1000mgとNA1500mgの併用により皮疹は消退した。症例2: 99歳女性。水疱性類天疱瘡に対するベタメタゾン内服治療中に副腎皮質ホルモン剤によるせん妄が出現した。オキサゾラム内服でせん妄はコントロールされたが,水疱性類天疱瘡の再燃時に副腎皮質ホルモン剤を増量したところせん妄が増悪した。TC1000mgとNA600mgを併用して副腎皮質ホルモン剤を減量することによりせん妄は軽減した。症例3: 91歳女性。水疱性類天疱瘡の再燃時にプレドニゾロンを増量したところ,消化管出血を起こしDICの状態に陥った。副腎皮質ホルモン剤を中止し,メシル酸ガベキサート点滴などの治療で全身状態は回復した。その後水疱が再発したが,TCとNAの内服で消退した。症例4: 75歳女性。脳梗塞の既往のため副腎皮質ホルモン剤は投与せず,TCとNAの内服を行い皮疹は消退した。過去の報告および自験例の経過よりTC/NA療法は中等症以下の水疱性類天疱瘡に対して有用と考えられた。また,副腎皮質ホルモン剤内服によるコントロール不良の水疱性類天疱瘡の場合,TCとNAの併用により副腎皮質ホルモン剤の減量を試みることも有用と思われた。

To determine whether serum soluble L-selectin (sL-selectin) levels are elevated in patients with systemic sclerosis (SSc) and whether serum sL-selectin levels change after treatment with lipo-prostaglandin E1 (lipo-PGE1), serum sL-selectin levels were examined by ELISA in patients with SSc (n=24), psoriasis vulgaris (n=22), and contact dermatitis (n=9), as well as normal control subjects (n=26). In five patients with SSc, serum sL-selectin levels were examined before and after intravenous injections of lipo-PGE1. Serum sL-selectin levels were significantly increased in patients with SSc (P

SUMMARYL-selectin is a leucocyte adhesion molecule involved in leucocyte interactions with vascular endothelial cells. Following leucocyte activation L-selectin is endoproteolytically released from the cell surface. To assess whether psoriasis vulgaris results in systemic leucocyte activation, we examined expression levels of L-selectin on subsets of peripheral blood leucocytes from patients with psoriasis (n = 25) and normal control subjects. Serum levels of soluble L-selectin were quantified by ELISA in patients with psoriasis (n = 75), pustulosis palmaris et plantaris, and contact dermatitis, as well as normal control subjects. Psoriasis severity was evaluated by psoriasis area and severity index (PASI). L-selectin expression levels on CD4+ T cells, B cells, monocytes, and neutrophils from patients with severe-type psoriasis (PASI ≥ 15) was significantly decreased compared with leucocytes from normal control subjects. Furthermore, L-selectin expression on CD4+ T cells showed good inverse correlation with PASI scores. Monocyte L-selectin expression was restored when the skin lesions of psoriasis were remitted. The frequencies of L-selectin+ CD4+ T cells or L-selectin+ CD8+ T cells from patients with psoriasis were almost normal. Serum L-selectin levels in patients with severe-type psoriasis were significantly higher than those in normal control subjects. These results suggest that subsets of leucocytes may be activated in psoriasis, and that L-selectin expression levels on some leucocyte subsets, especially CD4+ T cells, tend to correlate with disease severity of psoriasis.

The CD19 cell surface molecule regulates signal transduction events critical for B lymphocyte development and humoral immunity. Increasing the density of CD19 expression renders B lymphocytes hyper-responsive to transmembrane signals, and transgenic mice that overexpress CD19 have increased levels of autoantibodies. The role of CD19 in tolerance regulation and autoantibody generation was therefore examined by crossing mice that overexpress a human CD19 transgene with transgenic mice expressing a model autoantigen (soluble hen egg lysozyme, sHEL) and high-affinity HEL-specific IgMa and IgDa (IgHEL) antigen receptors. In this model of peripheral tolerance, B cells in sHEL/IgHEL double-transgenic mice are functionally anergic and do not produce autoantibodies. However, it was found that overexpression of CD19 in sHEL/IgHEL double-transgenic mice resulted in a breakdown of peripheral tolerance and the production of anti-HEL antibodies at levels similar to those observed in IgHEL mice lacking the sHEL autoantigen. Therefore, altered signaling thresholds due to CD19 overexpression resulted in the breakdown of peripheral tolerance. Thus, CD19 overexpression shifts the balance between tolerance and immunity to autoimmunity by augmenting antigen receptor signaling.

A 75-year-old Japanese man presented with pruritic blisters and macules on his trunk and extremities. He had been on hemodialysis for 4 years because of chronic renal failure, and in recent months, a polymethylmethacrylate membrane had been used for dialysis. After a change in dialysis membrane to a cellulose triacetate membrane, pruritic tense blisters developed on the extremities in combination with marked blood eosinophilia. Physical examination showed erythematous macules and tense blisters on the trunk and extremities. A biopsy specimen of an erythematous macule showed subepidermal vesicles and eosinophils that attached to the dermal-epidermal junction. Serum level of eosinophilic cationic protein was elevated. From clinical, histological, and immunological findings, a diagnosis of bullous pemphigoid was made. New blisters continued to erupt during the period in which the patient used the cellulose triacetate membrane dialyzer, and even after the use of clobetasol propionate. It resolved only after the patient came back to the use of a synthetic membrane dialyzer. We discontinued the use of clobetasol propionate, and neither bullous eruptions nor blood eosinophilia recurred. These observations suggest that cellulose membrane may be involved in the development of bullous pemphigoid through activation of eosinophils in the blood and the skin lesion, as in the present case.

A 34-year-old Japanese male had leg pain, edema of the legs, hypohidrosis, whorl-like opacities of the bilateral cornea, bilateral subcapsular cataracts, and chest discomfort on exercise. He had no characteristic angiokeratomas but did have telangiectases. The electrocardiogram revealed high voltage. The echocardiogram revealed mild mitral regurgitation. The alpha-galactosidase A activity in cultured lymphoblasts was deficient (0.5 nmol/h/mg protein). Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts. He had a G--> A transition at nucleotide 982 in the coding sequence of the alpha-galactosidase A gene which resulted in a glycine to arginine amino acid substitution at residue 328. His uncle also had leg pain, edema of the legs, hypohidrosis, and chest pain on exercise. He had no characteristic angiokeratomas but did have telangiectases. Cardiovascular examination revealed hypertrophic cardiomyopathy and stenoses of coronary arteries. Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts.

Melanoma and other benign or malignant pigmented skin tumors can significantly overlap in their clinical and dermoscopical presentations. Thus, pigmented skin lesions may be misdiagnosed in a large number of cases. An extensive review of the published work provides numerous examples of benign lesions mimicking melanoma. Although a number of melanocytic nevi may have been identified as melanomas, information about their clinical appearance is limited. In this report, we present the clinical appearances of two melanocytic nevi on the vulva and the upper extremity that were difficult to diagnose clinically. Detecting melanoma at an early stage is of the utmost importance. However, more attention should be given to the diagnostic accuracy of benign pigmented skin lesions, which otherwise may be diagnosed and treated as melanoma.

Bullous pemphigoid (BP), an autoimmune subepidermal-blistering disease of the elderly, is caused by antibodies against BP antigens at the epidermal basement membrane zone (BMZ). CD22 is a B lymphocyte specific response regulator, which is down-regulated after B-cell activation. Old CD22-deficient mice produce class-switched autoantibodies. To assess the role of CD22 in the pathogenesis of BP, we examined CD22 expression on B cells from BP patients and correlated its expression with clinical parameters. B cell expression of CD22 was 20% lower in BP patients when compared to healthy control subjects. In addition, B cells from BP patients showed decreased expression of L-selectin, which is an indicator of leukocyte activation, and CD22 expression levels were correlated with L-selectin expression. These results suggest that the decreased CD22 expression may be associated with the activation of B cells in BP. CD22 expression levels in BP patients did not correlate with the levels of anti-epidermal BMZ antibodies, and old CD22-deficient mice did not develop the anti-epidermal BMZ antibody. These results suggest that a decrease in CD22 expression may not be associated with BP-specific antibody production.

A 24-year-old woman with autoimmune thrombocytopenia and hypothyroidism had an inflammatory bullous eruption in the mouth, face, and trunk that left no milia or scars after healing. Histologic examination revealed a subepidermal bulla and a neutrophil infiltration. Direct immunofluorescence examination showed deposition of IgG and C3 in the basement membrane zone (BMZ). Indirect immunofluorescence examination with 1M sodium chloride-split skin showed IgG binding to the dermal side. Immunoblot analysis demonstrated IgG autoantibodies reacting with 290 kD dermal protein. We diagnosed this as epidermolysis bullosa acquisita (EBA) with a nonscarring inflammatory feature. Treatment with oral dapsone, 75 mg, and prednisolone, 20 mg, cleared the eruption. Reduction of the prednisolone dosage was associated with multiple erosions in the esophagus. Direct immunofluorescence examination revealed linear deposition of IgG in the esophageal BMZ. To our knowledge, this is the first report of EBA with esophageal involvement and deposition of IgG in the BMZ of the esophagus.

Although chemokines are critical elements for the selective attraction and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning T helper (Th) 1 or Th2 chemokines in autoimmune blistering disease (ABD). To determine whether serum levels of chemokines that are preferentially chemotactic for Th1 (monokine induced by IFN-gamma (MIG/CXCL9)) and Th2 (thymus and activation regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22)) cells were elevated and whether they correlated with the clinical features in patients with ABD. Serum chemokine levels were examined using ELISA in patients with pemphigus vulgaris (PV, n=19), pemphigus foliaceous (PF, n=14), or bullous pemphigoid (BP, n=27) and normal controls (n=20). Serum MIG levels were significantly higher in patients with PV, PF, or BP than those in the control subjects. Serum levels of TARC and MDC were also significantly elevated in patients with PV, PF, or BP relative to the normal controls. Among the ABD subgroups, the levels of each chemokine tended to be higher in BP patients than in PV patients. Furthermore, serum TARC levels correlated positively with serum IgE levels in patients with ABD. Levels of TARC, MDC, and MIG were significantly decreased after treatment when the skin lesions disappeared in these patients. Furthermore, serum MIG levels correlated positively with serum levels of TARC and MDC in the ABD patients. These results suggest that both a Th1 chemoattractant MIG and Th2 chemoattractants, TARC and MDC, cooperatively play a role in the development of ABD.

Skin fibrotic disorders such as systemic sclerosis (SSc) are characterized by an excessive production of extracellular matrix (ECM) and understood to develop under the influence of certain growth factors. Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that is implicated in various fibrotic disorders and induced in fibroblasts after activation with transforming growth factor-beta (TGF-beta). To better understand the mechanisms of persistent fibrosis seen in SSc, we previously established an animal model of skin fibrosis induced by exogenous application of growth factors. In this model, TGF-beta transiently induced subcutaneous fibrosis and serial injections of CTGF after TGF-beta caused persistent fibrosis. To further define the mechanisms of skin fibrosis induced by TGF-beta and CTGF in vivo, we investigated in this study, the effects of growth factors on the promoter activity of the proalpha2 (I) collagen (COL1A2) gene in skin fibrosis. For this purpose, we utilized transgenic reporter mice harboring the -17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase gene or a bacterial beta-galactosidase gene. Serial injections of CTGF after TGF-beta resulted in a sustained elevation of COL1A2 mRNA expression and promoter activity compared with consecutive injection of TGF-beta alone on day 8. We also demonstrated that the number of fibroblasts with activated COL1A2 transcription was increased by serial injections of CTGF after TGF-beta in comparison with the injection of TGF-beta alone. Furthermore, the serial injections recruited mast cells and macrophages. The number of mast cells reached a maximum on day 4 and remained relatively high up to day 8. In contrast to the kinetics of mast cells, the number of macrophages was increased on day 4 and continued to rise during the subsequent consecutive CTGF injections until day 8. These results suggested that CTGF maintains TGF-beta-induced skin fibrosis by sustaining COL1A2 promoter activation and increasing the number of activated fibroblasts. The infiltrated mast cells and macrophages may also contribute to the maintenance of fibrosis.

Background: Increased serum IgE levels are occasionally found in patients with severe bullous pemphigoid (BP). CD23, a low affinity Fc receptor for IgE, is mainly expressed on mature B lymphocytes. Studies have suggested that serum levels of soluble CD23 (sCD23) correlate with serum IgE levels and disease severity in BP. Objective: The purpose of our study is to examine whether the expression of CD23 is elevated in BP and whether this expression correlates with serum IgE levels and disease severity. Methods: We measured CD23 expression on B cells from patients with active BP, pemphigus vulgaris, pemphigus foliaceus, and atopic dermatitis (AD), as well as healthy control subjects, using a flow cytometer. Serum levels of IgE and sCD23 were also measured. Results: The expression of CD23 was significantly higher in BP patients compared with healthy control subjects (P

Studies have suggested that psoriasis vulgaris is mediated by type 1 T cells. In this study, we examined both chemokine receptor expression and intracellular cytokine production by circulating T cells to check the type 1/type 2 balance in psoriasis. CCR4+ and CXCR3- T cells predominantly produced interleukin-4 and interferon-gamma, respectively. The frequency of interferon-gamma-producing cells and that of CXCR3+ cells in circulating CD4+ T cells were similar for psoriatic patients and healthy control subjects. By contrast, the frequency of CCR4+CD8+ T cells and CCR4/CXCR3 ratio in circulating CD8- T cells were significantly higher in psoriatic patients than in healthy control subjects. Analysis of intracellular cytokine production also indicated relative increase of type 2 CD8+ T (Tc2) cells in peripheral blood from psoriatic patients. The frequency of circulating Tc2 cells directly correlated with Psoriasis Area and Severity Index. Immunohistochemical analysis showed that not only CXCR3+CD8+ T cells but also a similar number of CCR4+CD8+ T cells infiltrated the psoriatic epidermis and dermis. Our findings suggest an increase in Tc2 cell number in blood from psoriatic patients, and the association of Tc2 cells with inflammation in psoriasis.

ejd.2012.1667 Auteur(s) : Makoto Inaoki1 inaoki-m@kinbyou.hosp.go.jp, Chihiro Nishijima1, Bungo Ohyama2, Takashi Hashimoto2 1 Department of Dermatology, Kanazawa Medical Center, Shimoishibiki-machi Kanazawa, Ishikawa 920-8650, Japan 2 Department of Dermatology, Kurume University School of Medicine, Kurume, Japan An 86-year-old Japanese man presented with a one-week history of bullous lesions on the mouth, trunk and lower extremities. He had hypertension and had been treated with oral captopril for [...]

ejd.2011.1542 Auteur(s) : Yukari Yoshimura1, Chihiro Nishijima1, Kazuo Ikeda2, Keiko Ikeda3, Yo Niida4, Makoto Inaoki1 inaoki-m@kinbyou.hosp.go.jp 1 Department of Dermatology 2 Department of Orthopedic Surgery 3 Department of Cardiology, National Hospital Organization Kanazawa, Medical Center, Kanazawa, 1-1 Shimoishibiki-machi, Ishikawa 920-8650, Japan 4 Medical Genetics Center, Kanazawa Medical University Hospital, Ishikawa, Japan The vascular type of Ehlers-Danlos syndrome (EDS type IV, EDS-IV) [...]

The CD22 cell-surface adhesion molecule is capable of modulating B lymphocyte antigen receptor (BCR)-mediated signals, as well as the generation of BCR-independent signals. Within the cytoplasmic domain of CD22 are motifs that are structurally homologous to known activation and inhibitory motifs. These motifs demonstrate physiologic significance via associations with known effector proteins that likely mediate their corresponding inhibitory and activation roles. Furthermore, the targeted deletion of CD22 in mice results in phenotypic changes and alterations in BCR-mediated signal transduction that are consistent with both positive and negative roles for CD22 in B cell development and activation.

CD19 is a component of a cell surface receptor complex that regulates B lymphocyte responses to transmembrane signals including those generated through the B cell antigen receptor. Studies in mice which lack or overexpress CD19 show that changes in CD19 expression levels have significant effects on B cell development and function. Recent studies suggest that CD19 establishes a Src-family kinase activation loop that amplifies tyrosine phosphorylation of numerous downstream effector molecules including potentially positive and negative regulatory elements. These observations provide an understanding of how CD19 governs the molecular ordering and intensity of signals transduced through multiple B cell receptors.

Some cytokines have been suggested to take part in the blister formation in bullous pemphigoid (BP). However, the roles of the cytokines are only partly understood. To elucidate the involvement of cytokines in the immunological mechanisms in BP, we investigated the serum levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-13, soluble IL-2 receptor and soluble CD23 in patients with BP, and the correlation between cytokine levels and other clinical and laboratory data. Serum levels of these cytokines and soluble receptors were determined by enzyme-linked immunosorbent assay in 19 patients with BP and in 16 normal control subjects. Serum levels of IL-5 (P < 0.0001), IL-6 (P < 0.01) and IL-8 (P < 0.05) were significantly higher in BP patients than in the control subjects. Other cytokines and soluble receptor levels were not significantly different. Serum levels of IL-6 (P < 0.05) and IL-8 (P < 0.05) were significantly decreased after treatment when skin lesions disappeared. These results suggest that serum levels of IL-6 and IL-8 could be indicators of disease activity of BP.

B cell activation following antigen receptor cross-linking can be augmented in vitro by ligation of cell surface CD22, which associates with the SHP1 protein tyrosine phosphatase. The targeted deletion of CD22 in mice demonstrated that CD22 differentially regulates antigen receptor signaling in resting and antigen-stimulated B lymphocytes. B cells from CD22-deficient mice exhibited the cell surface phenotype and augmented intracellular calcium responses characteristic of chronically stimulated B cells, as occurs in SHP1-defective mice. Thus, CD22 negatively regulates antigen receptor signaling in the absence of antigen. However, activation of CD22-deficient B lymphocytes by prolonged IgM cross-linking resulted in modest B cell proliferation, demonstrating that CD22 positively regulates antigen receptor signaling in the presence of antigen.

The authors report a case of Werner's syndrome complicated by quintuplicate malignancy, and review the literature data. Four malignancies occurred synchronously in the case: osteosarcoma of the left distal tibia, malignant melanoma of the left plantar region, gastric cancer, pulmonary coin lesion. The osteosarcoma and malignant melanoma were treated by below-knee amputation and the gastric cancer by palliative surgery; the pulmonary coin lesion did not respond to cisplatin chemotherapy. It was difficult to treat the multiple primary cancer curatively, and patient died of respiratory failure due to a brain tumor seven months after surgery. The postmortem examination revealed a papillary carcinoma of the thyroid gland and a leiomyosarcoma of the lung. In some cases of Werner's syndrome, attention should be paid to the concurrent occurrence of multiple primary malignant neoplasms.