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Granulation tissue formation is required for the healing of deep pressure ulcers. The wound healing process is often delayed at the stage of granulation tissue formation. The pathogenesis of pressure ulcers showing granulation tissue may vary; however, no terminology has been defined to describe existing ulcers. Thus, we previously defined terminology for granulation tissue to describe individual ulcers. Based on these terms, we retrospectively evaluated the findings of deep pressure ulcers. In particular, we focused on polypoid granular tissue, a unique morphological feature. Polypoid granulation tissues were frequently observed in pressure ulcers over the sacrum compared with those over the foot. Chronological observation of a few cases indicated that external forces from specific directions during the healing process caused the development of polypoid granulation tissue. In addition, most pressure ulcers showing polypoid granulation tissue exhibited a trench-like appearance in individual wounds. Based on these observations, polypoid granulation tissue may generate from specific external forces, which lead to wound deformity. Morphological findings in an individual wound may be useful to predict the mechanical factors on existing pressure ulcers.

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.

Mycosis fungoides usually follows an indolent clinical course. We report here a rapidly progressive case of mycosis fungoides with peculiar clinical and histological features, presenting as a haematoma-like mass on the thigh accompanied by multiple reddish brown erythematous lesions on the trunk and extremities. Histopathologically, the erythematous lesions showed epidermotropism of atypical T lymphocytes expressing CD4 and prominent syringotropism without syringometaplasia. The haematoma-like lesion consisted of diffuse and dense infiltrates of medium-to-large-sized pleomorphic lymphocytic cells expressing CD30, suggesting that CD30+ large-cell transformation had occurred. Mycosis fungoides presenting as a haematoma-like lesion is rare and may be a poor prognostic sign.

Eighteen patients with adult-onset Still's disease have been followed up for 3-22 years in our department. Initial manifestations were fever with skin rash in 14 patients, fever, skin rash and sore throat in two, skin rash in one and arthralgia in one. During the follow-up period, typical skin rash was seen in all patients, of them five patients (29%) revealed atypical skin rash simultaneously. Atypical rash included persistent erythema with pigmentation in two, persistent plaques and papules with linear erythema in two and edema of the eyelids mimicking dermatomyositis in one. Persistent papules and plaques revealed histologically characteristic features, such as dyskeratotic keratinocyte and liquefaction degeneration as well as a sparse superficial dermal infiltrate containing scattered neutrophils. In patients of chronic articular type and polycyclic systemic type, atypical skin rash, lymphadenopathy and hyperferritinemia were noted to be significantly higher than those of monocyclic type. These factors might be prognostic factors of adult-onset Still's disease in our study.

We describe an unusual xeroderma pigmentosum (XP) patient with a mutation in XP complementation group G, representing only the third reported Japanese XP-G patient. A 40-year-old men (XP3HM), born from consanguineous parents experienced sun sensitivity and pigmentary changes of sun-exposed skin since childhood. He developed a squamous cell carcinoma on his lower lip at the age of 40. He has neither neurological abnormalities nor Cockayne syndrome. The primary fibroblasts of the patient were hypersensitive to killing by UV (D0 = 0.6 J/m2) and the post-UV unscheduled DNA synthesis was 8% of normal. Host cell reactivation complementation analysis implicated XP complementation group G. We identified a novel homozygous mutation (c.194T>C) in a conserved portion of the XPG(ERCC5) gene, resulting in a predicted amino acid change; p.L65P. We confirmed that this genetic change reduced DNA repair thus linking this mutation to increased skin cancer.

Recurrent digital ulcers are manifestations of vascular disease in patients with systemic sclerosis (SSc). We report six patients with severe digital ulcers who were treated with bosentan administered p.o., 62.5-125 mg daily. The mean duration from the diagnosis of SSc to the initiation of bosentan was 9.5 years, and the observation period after bosentan administration was from 7 months to 4.5 years. In case 1, neither new digital ulcers nor Raynaud's phenomenon developed for 4.5 years. In case 2, digital ulcers recurred after the discontinuation of bosentan; however, re-administration of bosentan lead to the improvement. In cases 3-5 with recurrent digital ulcers, no new lesions have developed. In these five patients, pain evaluated by visual analog scale was significantly reduced. In three patients, bosentan was discontinued because of severe liver dysfunction. These results suggest that bosentan is an effective treatment for refractory digital ulcers associated with SSc; however, liver function should be carefully monitored. Compared to the doses of bosentan used to treat pulmonary hypertension, relatively lower doses may effectively control painful digital ulcer/gangrene in patients with SSc.

Nephrogenic systemic fibrosis (NSF) is a fibrotic disease that presents with a history of renal dysfunction. The differential diagnosis generally includes scleromyxedema, systemic sclerosis, and morphea. Especially, scleromyxedema can be extremely difficult to distinguish microscopically. Although the fibrocytes in NSF are often positive for CD34 and procollagen-I, this is not specific for NSF. We identified positive iron staining in the skin of a patient with NSF and investigated whether this was a specific feature among 9 patients with NSF reported in Japan. We found that 6 of 9 patients showed positive iron staining in the dermal fibrocytes. The amount of iron deposition seemed to have no correlation with the degree of fibrosis or duration of the skin lesions but correlated with apparent history of the use of gadolinium-based contrast agents. As controls, skin biopsies from patients with scleromyxedema, morphea, and systemic sclerosis were evaluated by iron staining. None of these control patients showed iron deposition, indicating that positive iron staining may be specific to NSF and can be a useful tool for NSF diagnosis.

Arteriovenous malformation (AVM) is a structural vascular abnormality with no proliferation of cellular components. We report on a 53-year-old man who presented with a 15-year history of a progressively enlarging nodule on his lower lip. A dark-reddish, easy-bleeding nodule diagnosed as AVM was resected to reduce the volume and troublesome bleeding. Histologically, the nodule revealed that the proliferating cellular area was composed of endothelial cells and pericytes in addition to the area of dilated vessels. We speculated that the cell proliferation developed secondary to AVM. We also discuss the histological differential diagnosis of spindle cell hemangioma and pseudo-Kaposi's sarcoma.

Cutaneous adverse effects of imatinib mesylate (Glivec ® ) are common and various types of skin eruptions have been reported. We report here a 57-year-old man who presented with lichen planus-like lesions on his extremities and palmoplantar hyperkeratosis due to the use of imatinib mesylate for chronic myeloid leukaemia. The skin lesions improved after discontinuation of imatinib mesylate but re-administration of the drug at a lower dose provoked a mild recurrence. He could, however, continue to take the drug at the lower dose and his skin lesions were well-controlled by topical corticosteroid treatment. The literature on lichenoid drug eruption due to imatinib mesylate is reviewed.

Livedoid vasculopathy (LV) is thought to be a thrombogenic disorder. Here, we report a case of LV presenting livedo reticularis with leg ulcers clinically and many thrombogenic cutaneous vessels histologically. These features strongly suggested the presence of thrombogenic factors involved with the development of the lesions. After examination of various possible thrombogenic factors including phosphatidylserine-dependent anti-prothrombin antibody, we failed to detect any responsible thrombogenic factors for this case of LV. Recently, diverse thrombogenic factors have been reported to be involved in LV. This case may suggest that unknown thrombogenic factors are additionally related to LV pathogenesis.

We report a 29-year-old woman with a 15-year history of recurrent pruritic urticarial erythemas. The individual lesions lasted for > 24 h, and antihistaminic agents were not effective. Histological examination of a skin biopsy revealed interstitial oedema of the dermis and perivascular infiltration of numerous eosinophils without vasculitis. No internal organ involvement or peripheral blood eosinophilia was present. A diagnosis of persistent urticaria was made and the patient was successfully treated with oral corticosteroid therapy. Persistent urticaria has been described as an unusual reaction that lasts longer than typical urticaria. It is effectively treated with corticosteroids, but not with antihistaminic agents. In order to choose the most effective treatment, persistent urticaria should be recognized as a different clinical condition from typical urticaria.

Purpura and livedo are common cutaneous manifestations of microscopic polyangiitis (MPA); however, only a few clinical analyses focusing on the relationship between clinical symptoms and the affected vessels in the skin have been reported. We herein report the cutaneous manifestations and histological features of four patients with MPA. In two patients, a Henoch-Shönlein purpura-like eruption developed with necrotizing vasculitis localized in the upper dermis. The other two patients presented with livedo racemosa; with histological findings of necrotizing vasculitis of the small vessels around the muscle fibers or from the deep dermis to subcutaneous tissue. Two patients' cases were complicated by systemic sclerosis and had poor prognoses. MPA can present with various cutaneous manifestations. Additional research is required to ascertain the relationship between the prognosis and the affected vessels.

A 67-year-old woman was referred to our department with a 1-month history of facial exanthemas. She had been diagnosed as having acute monocytic leukemia (French-American-British classification, M5b) based on the histological findings of bone marrow. Physical examination revealed diffuse edematous erythema on her cheeks, eyelids and glabella with scattered reddish papules. Histological examination demonstrated dense infiltration of atypical mononuclear cells in the dermis. Specific cutaneous lesions could occur in acute monocytic leukemia more frequently than in other types of leukemia, but rarely show symmetrical edematous erythema limited to the face.

We report a 32-year-old woman with a 12-year history of systemic lupus erythematosus. Physical examination revealed indurated plaques with small ulcers on her extremities and trunk, which were histologically diagnosed as lupus erythematosus profundus. On her arms and knees, multiple small calcified nodules were noted in the dermis and subcutis. An elevated level of anti-phosphatidylserine/prothrombin antibodies was noted. She had been suffering from digital ulcers on the left fourth finger. Despite conservative therapies, new ulcers appeared on other fingers. After the administration of bosentan, no new lesion has developed. Bosentan, recognized as a choice of treatments for digital ulcers in systemic sclerosis, is worth trying in systemic lupus erythematosus patients with refractory digital ulcers.

Summary Background As Bowen’s disease of the nail apparatus is quite rare, there have been only a few reports on the prevalence of human papillomavirus (HPV) infection in this condition. Objectives The purpose of this study was to clarify the association of HPV with this disease involving the nail apparatus. Methods Five patients with Bowen’s disease of the nail apparatus were investigated clinically, virologically and histologically. Total DNAs extracted from excised skin lesions were analysed using polymerase chain reaction (PCR) for the presence of HPV DNA and the amplified products were subjected to DNA sequence analyses. Histological localization of HPV DNA was examined by in situ hybridization. Results In three of five patients, HPV was detected by PCR amplification, and subsequent sequence analyses of the PCR products showed the sequences of HPV type 56. A common clinical feature of the three HPV-positive patients was longitudinal melanonychia. In contrast, the two HPV-negative patients presented with a convex nail deformity and a periungual ulcerative lesion. In two of three positive cases, there was a silent point mutation in the L1 gene of each HPV. In the remaining one case, the nucleotide sequence was consistent with the consensus sequence of HPV 56. Sequence analyses of the E6 gene revealed the infection of different variants of HPV 56 among the three cases. The viral genomes were located in keratinocyte nuclei upon in situ hybridization. Conclusions HPV 56 may be involved in the carcinogenesis of Bowen’s disease affecting the nail matrix with longitudinal pigmentation.

We report a 72-year-old man with nevoid basal cell carcinoma syndrome (NBCCS) who presented with 25 skin cysts on his trunk and extremities. Fourteen of 25 skin cysts (56%) were observed on his hands. Histological examination demonstrated that most of the excised cysts had an epithelial wall with typical epidermal keratinization. However, 4 skin cysts (4/16; 25%) showed a corrugated or festooned inner surface of wall without a granular cell layer, which resembled an odontogenic keratocyst, a characteristic feature of skin cysts in NBCCS. A review of the literature suggested that acral localization of skin cysts is a distinctive feature of NBCCS. In addition, the histological findings of skin cysts resembling an odontogenic keratocyst might be a hallmark of NBCCS.

We report an autopsy case of a 60-year-old Japanese woman who died 27 years after the onset of systemic sclerosis and 4 years after the diagnosis of pulmonary arterial hypertension. Oral administration of bosentan was effective in improving her dyspnea but had to be stopped because of drug eruption along with fever and eosinophilia. During hospitalization for the treatment of multiple skin ulcers and gangrene, she suddenly complained of severe respiratory difficulty, followed by bradycardia, unconsciousness and cardiopulmonary arrest. The autopsy revealed concentric intimal proliferation and marked luminal obstruction in many small- and medium-sized vessels of the lungs. In addition to right ventricular hypertrophy and dilatation, similar vascular changes were also present in the myocardial tissue and the atrioventricular node. In our patient, these marked vascular changes caused pulmonary hypertension followed by the severe right heart failure. The vascular changes in the atrioventricular node were suspected as the cause of a fatal arrhythmia leading to sudden death.

Juvenile or childhood onset systemic sclerosis (SSc) is rare. In our department, we encountered three juvenile SSc patients among the overall 206 SSc patients. All three cases were diffuse cutaneous type SSc (dSSc) with positive antinuclear antibodies. In this report, we report the three patients and analyze clinical and serological features of 58 Japanese patients with juvenile SSc. Forty-eight patients (92.3%) were classified as dSSc and 21 out of 35 patients (60%) had anti-topoisomelase I antibodies, while anticentromere antibodies were not detected in any patients. Prevalence of lung fibrosis and scleroderma renal crisis was low, however, the rate of cardiac involvement was higher than that in adult patients.

We reported two patients with refractory eosinophilic fasciitis (EF) and provided a systematic review of the literature to determine the clinical variables associated with prognosis of EF. We enrolled 88 cases, whose clinical characteristics were analyzed by separating the patients into two or three groups based on outcome. The incidence of certain clinical and pathological features differed among the groups. In particular, the incidence of morphea-like skin lesions in patients with refractory fibrosis was significantly higher than in patients without refractory fibrosis (p = 0.003). Patients with morphea-like skin lesions were 1.9 times more likely to develop persistent fibrosis than patients without these lesions (95% confidence intervals, 1.5-2.5). A younger age (under 12 years) at onset was associated with a 1.6 times greater risk of residual fibrosis (95% confidence interval, 1.1-2.2). Trunk involvement was associated with a 1.4 times greater risk of residual fibrosis (95% confidence interval, 1.0-2.0). Histopathologically, the presence of dermal fibrosclerosis was associated with a 1.4 times greater risk of refractory fibrosis (95% confidence interval, 1.0-2.1). We consider these clinical characteristics, notably the presence of morphea-like skin lesions may be an important risk factor for developing residual fibrosis in EF patients.

The treatment of severe lymphedema is a difficult challenge. We performed lymphaticovenular anastomosis on two patients with secondary skin lesions of chronic lymphedema; one patient exhibited acquired lymphangioma circumscriptum of the vulva and the other presented elephantiasis nostras verrucosa of the lower leg. Both patients obtained a remarkable improvement in skin lesions and also in the reduction of lymphedema of the lower extremity. During a 6-month-follow-up period, constant reduction in the circumference of the lower extremities without exacerbation of skin lesions was achieved in both patients. Lymphaticovenular anastomosis is a useful surgical treatment for secondary lymphedema in the lower extremities. In addition, this surgical treatment is effective for secondary lesions of lymphedema, including acquired lymphangioma circumscriptum and elephantiasis nostras verrucosa.

Summary Background Although digital ulcerations frequently occur in patients with systemic sclerosis (SSc), there have been few reports on the macrovascular involvement. Objectives To evaluate the macrovascular involvement in patients with SSc exhibiting digital ulceration or gangrene. Methods Transfemoral catheter arteriography of the upper and/or lower extremities was performed in eight patients (one man and seven women, age range 42–71 years) with SSc exhibiting digital ulceration or gangrene. The background of the patients, such as autoantibody profiles and vascular risk factors including smoking habits, was also investigated. Results Macrovascular involvement was detected in seven of eight patients. In three of seven patients who underwent arteriography of the upper extremity, occlusion was limited to the digital arteries. Obliteration of the ulnar artery and superficial palmar arch was detected in three of seven patients, and the radial artery in one patient. Only one of five patients who underwent arteriography of the lower extremity showed the occlusion limited to digital arteries of the foot. Occlusion of the posterior tibial artery, dorsalis pedis artery and arcuate artery was detected, each in one patient. Two patients showed occlusion of the plantar arch. Overall, the occlusion of arteries proximal to the digits was demonstrated in four of eight patients. Three of the four patients were positive for antitopoisomerase-1 antibody and had diffuse cutaneous SSc (dcSSc) with multiple skin ulcers or gangrene. Conclusions Macrovascular involvement as detected with arteriography is not rare in SSc patients with digital ulceration or gangrene. Moreover, the vascular occlusion proximal to the digits seemed to be frequent in antitopoisomerase-1 antibody-positive dcSSc patients with multiple skin ulcers or gangrene.

We present a 79-year-old man who suffered from extramammary Paget's disease (EMPD) with bowenoid histological features accompanied by an ectopic EMPD lesion on his abdomen. He had had an erythematous plaque on his genital region for three years. Based on a biopsy specimen, he was referred to our hospital with the histological diagnosis of Bowen's disease. The histological findings of the genital lesion obtained by surgical resection showed typical areas of Paget's cells adjacent to areas characteristic of Bowen's disease. Immunohistochemical findings showed CEA and CK7 positive tumor cells in both areas, so the atypical cells showing the bowenoid pattern could be regarded as tumor cells of Paget's disease. Immunohistochemical staining for CEA and CK7 along with multiple biopsies can be helpful in making the diagnosis of Paget's disease with bowenoid histologic features.

Episodic angioedema associated with eosinophilia (EAE) is characterized by recurrent episodes of edema, eosinophilia in peripheral blood, urticaria, fever, and weight gain [1]. Non-episodic angioedema associated with eosinophilia (NEAE) has been reported as a single episode of angioedema that was responsive to treatment of low-dose corticosteroids or antihistamines [2].A 41-year-old Japanese woman noted urticaria and swelling in both lower legs in September 2011. The swelling extended to hands and [...]

We report an autopsy case of delayed anaphylactic shock due to contrast medium. A 17-year-old Japanese man underwent angiography using non-ionic contrast medium under the suspected diagnosis of Buerger’s disease. Initial symptoms appeared 6 h after the administration of the contrast medium, and death was confirmed 11 h later. Considering the clinical course and the results of the autopsy, we concluded that the direct cause of the patient’s death was severe acute circulatory failure due to a delayed allergic reaction to the contrast medium. The reported incidence of serious delayed reactions or biphasic reactions to non-ionic contrast medium is extremely low; however, we should be aware of such rare adverse reactions.

We report a 6-year-old boy with unilateral generalized morphea distributing on the right side of his lower leg, trunk, and upper arm. A skin biopsy from the right thigh showed accumulation of thick collagen bundles extending from the middle dermis to the subcutaneous fat tissue. The levels of antinuclear antibodies, rheumatoid factor, and anti single-stranded DNA antibody were elevated. No severe deformity or functional disabilities were noted. With topical corticosteroid therapy, the sclerotic skin became gradually softer, and no progression of sclerosis has been noted for one year.

16歳,女性。初診1週間前より四肢に紅色皮疹が出没,また,関節痛,関節腫脹,咽頭痛も出現した。皮疹は拇指頭大までの淡紅色の不整形紅斑であり,四肢に多発し融合傾向を認めた。ロキソプロフェンナトリウム内服にて一時改善するも,その後39℃台までの間欠熱が出現,肝機能異常を認めるとともに血清フェリチン値が高値となった。プレドニゾロン20mg投与にて軽快し,1年半経過した現在まで再発を認めない。フェリチン値は病勢との相関を認めた。

A pressure ulcer is defined as damage to skin and other tissues over a bony prominence caused by excess pressure. Deep pressure ulcers that develop over specific bony prominences often exhibit wound deformity, defined as a change in the 3-dimensional shape of the wound. Subsequently, the wound deformity can result in undermining formation, which is a characteristic of deep pressure ulcers. However, to date, a concept with respect to alleviating wound deformity has yet to be defined and described. To clarify the issue, we propose a new concept called "wound fixation" based on the physical properties of deep pressure ulcers with wound deformity. Wound fixation is defined here as the alleviation of wound deformity by exogenous materials. The wound fixation methods are classified as traction, anchor, and insertion based on the relation between the wound and action point by the exogenous materials. A retrospective survey of a case series showed that wound fixation was preferentially used for deep pressure ulcers at specific locations such as the sacrum, coccyx, and greater trochanter. Moreover, the methods of wound fixation were dependent on the pressure ulcer location. In conclusion, our new concept of wound fixation will be useful for the practical treatment and care of pressure ulcers. Further discussion and validation by other experts will be required to establish this concept.

Dear Editor, A 33-year-old Japanese woman first visited our department in 1999 at the age of 24 years with a 5-year history of Raynaud’s phenomenon and finger stiffness. Physical examination revealed skin sclerosis of her fingers, forearms, face, chest and thighs. Her modified Rodnan’s skin score was 32. She was diagnosed as having a diffuse cutaneous type of systemic sclerosis. Serological tests detected antinuclear antibodies (1:1280, homogenous and nucleolar pattern) and positive anti-Topoisomerase I antibodies. Other autoantibodies including anti-centromere, U1-RNP, SS-A ⁄B, and Sm antibodies were all negative. She was treated with prednisolone (PSL) 20 mg ⁄day and bucillamine 100 mg ⁄day due to the worsening of her skin sclerosis. At that time, she had mild reflux esophagitis but no interstitial pneumonia nor pulmonary hypertension. In 2001, interstitial pneumonia was detected. In 2004, she was given four courses of cyclophosphamide pulse therapy. In January 2007, the interstitial pneumonia was worsening, so methylprednisolone pulse therapy was performed and PSL was increased to 60 mg ⁄day. Azathioprine 100 mg ⁄day was added in March 2007, as the dose of PSL was tapered. Interstitial pneumonia was improved, though slight shadows in the lower lung fields remained on the chest roentgenogram. The dose of PSL was gradually tapered to 13 mg ⁄day and no recurrence of interstitial pneumonia was

A 32-year-old Japanese man presented with a 3-year history of purple reddish, and painful swelling of his fingers along with indurated erythema on his nose and ears. He was diagnosed as having sarcoidosis 8 years prior because of uveitis and bilateral hilar lymphadenopathy. X-rays of the hands revealed multiple cystic lesions in the phalanges. Histological examination of the ear revealed epithelioid cell granulomas in the dermis. Oral prednisolone 20 mg/day improved his finger swelling and pain; however, his finger deformities and erythema remain unchanged. Bone involvement is sometimes seen in sarcoidosis and the hands are the most frequently affected areas. The frequency of bone involvement is higher in lupus pernio in comparison with other types of skin sarcoidosis. Systemic corticosteroids could be the first choice of treatment to relieve the symptoms.

A 5-year-old girl presented with a two-month-history of skin rash and general fatigue. She had a slight fever, progressive muscle weakness and liver dysfunction. Gottron's papules on her fingers and purple-reddish papules on her elbows were noted. Serum aldolase levels were highly elevated, however, creatine phosphokinase levels were normal. An MRI revealed abnormal high signal changes in her gluteus minimus muscles. Interstitial pneumonia suddenly developed and she died despite aggressive treatment with methylprednisolone pulse therapy followed by intravenous administration of cyclophosphamide, immunoglobulin and cyclosporine A. Interstitial pneumonia is rare in juvenile dermatomyositis; however, as in adult cases, it can be fatal. In order to prevent severe complications and functional disabilities, early aggressive treatments should be considered when muscle inflammation is refractory to ordinary treatment.

We report a 66 year-old Japanese man with Fournier's gangrene developed from pressure ulcers. Pelvic computed tomography (CT) scan confirmed subcutaneous gas accumulation from the scrotum to the gluteal region. Emergent debridment and the administration of systemic antibiotics improved the symptoms. Fournier's gangrene is a necrotizing fasciitis of the perineal and genital region. Proper treatment for bacterial infection in pressure ulcers is critical and clinicians should be alert to early signs of necrotizing fasciitis.

We report here the case of a 55-year-old Japanese man with a one-year history of multiple ulcers on the left crural region. He had had pronounced varicose veins on both legs and the abdominal region for 35 years. Computed tomography images of the thoracic and abdominal regions showed the absence of an inferior vena cava, with pronounced dilatation of paravertebral venous plexus, cutaneous and azygous veins. Conservative topical treatments led to complete healing of the ulcers in one month. An absent inferior vena cava is an uncommon abnormality, often complicated by cardiac and other visceral malformations. It is a rare cause of chronic leg ulcers.

We report a female patient with dermatomyositis whose erythematous lesions were successfully \ntreated with topical tacrolimus. In spite of the usually good response of muscle symptoms to systemic \ncorticosteroid, the skin lesions of dermatomyositis often remain resistant to conventional therapy. The \nskin lesions of our patient were markedly improved after four weeks of topical application of tacrolimus. \nThe clinical efficacy of tacrolimus has been described for other skin disorders, but tacrolimus ointment \nis also useful for treating the skin lesions of dermatomyositis.

We present the case of a 60-year-old female patient with systemic sclerosis complicated by pulmonary hypertension. Ten days after the initiation of treatment with bosentan, high fever and skin eruptions were noted. In the previous reports, the frequency of drug-induced skin eruptions has not been well documented. Since the use of bosentan is expected to increase, we should be aware of the previously unknown adverse effects as well as skin eruptions.

Background and Aims : We investigated histopathological differences between granuloma pyogenicum (GP), intradermal (IGP) and subcutaneous (SGP) granuloma pyogenicum. Methods : Twenty cases of GP, one case of IGP and one case of SGP were immunohistochemically studied for the expression of CD34 and Factor VIII-related antigen (F VIII-RA). Results : Immunohistochemistry for CD34 demonstrated various staining patterns in GP, IGP and SGP. F VIII-RA was expressed immunohistochemically in GP, but staining was completely absent in IPG and SPG. Conclusions : These results suggested that immunohistochemical difference among these tumors might reflect the degree of maturation in neoplastic endothelial cells.

Eighteen patients with adult-onset Still's disease have been followed up for 3-22 years in our department. Initial manifestations were fever with skin rash in 14 patients, fever, skin rash and sore throat in two, skin rash in one and arthralgia in one. During the follow-up period, typical skin rash was seen in all patients, of them five patients (29%) revealed atypical skin rash simultaneously. Atypical rash included persistent erythema with pigmentation in two, persistent plaques and papules with linear erythema in two and edema of the eyelids mimicking dermatomyositis in one. Persistent papules and plaques revealed histologically characteristic features, such as dyskeratotic keratinocyte and liquefaction degeneration as well as a sparse superficial dermal infiltrate containing scattered neutrophils. In patients of chronic articular type and polycyclic systemic type, atypical skin rash, lymphadenopathy and hyperferritinemia were noted to be significantly higher than those of monocyclic type. These factors might be prognostic factors of adult-onset Still's disease in our study.

Aims The cutaneous manifestation of IgG4-related disease has rarely been reported. The aim of this study is to identify and describe the cutaneous manifestations associated with IgG4-positive plasma cell infiltration in the skin. Methods The authors investigated two cases of IgG4-related disease with solitary skin lesions and compared the immunohistochemical characteristics of infiltrating cells among IgG4-related disease, Kimura's disease and cutaneous pseudolymphoma. Results IgG4-related disease manifested as an indurated plaque on the anterior chest in one case and a nodule on the toe in the other case. Histopathologically, skin lesions of IgG4-related disease showed a dense, mixed-cell infiltrate containing lymphocytes, plasma cells and eosinophils along with fibrosis. Plasma cells stained positively with anti-IgG and anti-IgG4 antibodies, and the ratio of IgG4+/IgG+ cells was more than 50%. Serum levels of IgG and IgG4 were not elevated and no lesions were found in other organs. Skin samples taken from Kimura's disease showed histopathological features similar to those of IgG4-related disease. The proportion of IgG4+/IgG+ was high in Kimura's disease, but not in cutaneous pseudolymphoma. Conclusions The solitary skin lesions of IgG4-related disease were similar histologically and immunohistochemically to the skin lesions of Kimura's disease. The concept of IgG4-related disease may help clarify the pathomechanism of diseases of unknown aetiology that possess features of IgG4-related disease.

We report an autopsy case of delayed anaphylactic shock due to contrast medium. A 17-year-old Japanese man underwent angiography using non-ionic contrast medium under the suspected diagnosis of Buerger's disease. Initial symptoms appeared 6 h after the administration of the contrast medium, and death was confirmed 11 h later. Considering the clinical course and the results of the autopsy, we concluded that the direct cause of the patient's death was severe acute circulatory failure due to a delayed allergic reaction to the contrast medium. The reported incidence of serious delayed reactions or biphasic reactions to non-ionic contrast medium is extremely low; however, we should be aware of such rare adverse reactions.

We report the first Japanese patient with primary cutaneous histoplasmosis who was infected inside Japan. He was not an immunocompromised host but his cutaneous lesions developed on preexisting papuloerythroderma (Ofuji). The long-term topical corticosteroid treatment for papuloerythroderma, which could have suppressed the local immunological defence system of the skin, might have been responsible for the histoplasma infection in the present case.

Recurrent digital ulcers are manifestations of vascular disease in patients with systemic sclerosis (SSc). We report six patients with severe digital ulcers who were treated with bosentan administered p.o., 62.5-125 mg daily. The mean duration from the diagnosis of SSc to the initiation of bosentan was 9.5 years, and the observation period after bosentan administration was from 7 months to 4.5 years. In case 1, neither new digital ulcers nor Raynaud's phenomenon developed for 4.5 years. In case 2, digital ulcers recurred after the discontinuation of bosentan; however, re-administration of bosentan lead to the improvement. In cases 3-5 with recurrent digital ulcers, no new lesions have developed. In these five patients, pain evaluated by visual analog scale was significantly reduced. In three patients, bosentan was discontinued because of severe liver dysfunction. These results suggest that bosentan is an effective treatment for refractory digital ulcers associated with SSc; however, liver function should be carefully monitored. Compared to the doses of bosentan used to treat pulmonary hypertension, relatively lower doses may effectively control painful digital ulcer/gangrene in patients with SSc.

Hydroxyzine is a first-generation antihistamine agent. It is clinically used as a mild tranquillizer as well as an antihistamine. It is widely administered to many patients, intravenously or intramuscularly, as a pre-anesthetic medication, sedative or antipruritic agent [1]. Adverse events caused by hydroxyzine are rare and include drowsiness, dry mouth, local pain, etc. [2]. When intramuscularly-given hydroxyzine leaks into intradermal and/or subcutaneous tissue, the skin structure is damaged. Therefore, [...]