Deposition of elafin in the involved vascular wall of neutrophil-mediated cutaneous vasculitis.

BACKGROUND: Neutrophil elastase plays an important role in skin inflammation induced by neutrophil infiltration. Elafin is an inducible elastase inhibitor expressed by keratinocytes, and is known to be involved in pathogenesis of neutrophilic skin disorders such as psoriasis. METHODS: Immunohistochemical studies of elafin expression in the cases of vasculitis were performed. Induction of elafin expression in cultured vascular cells and its effect on neutrophil migration were studied in vitro. RESULTS: A positive immunoreactivity was detected in polyarteritis nodosa, giant cell arteritis and Schönlein-Henoch purpura, but no immunoreactivity was found in Churg-Strauss syndrome. Elafin expression in cultured venous endothelial cells and arterial smooth muscle cells was undetectable, but induced by interleukin-1ß (IL-1ß) and IL-8. Elafin inhibited the elastin peptide-induced neutrophil chemotaxis at the concentration of 10(-8) -10(-5) mol/L. CONCLUSION: Elafin deposition induced by cytokines (IL-1ß or IL-8) will be an important regulator for the progress of leucocytoclastic vasculitis by functioning as an inhibitor for neutrophil chemotaxis as well as for vascular elastin degradation.

First Report of Clubroot on Capsella bursa-pastoris Caused by Plasmodiophora brassicae in Sichuan Province of China.

Shepherd's purse (Capsella bursa-pastoris (L.) Medicus) is an edible and wild medicinal plant widely distributed in China. This plant has been cultivated in Shanghai, China, since the end of the 19th century. Infection of C. bursa-pastoris by Plasmodiophora brassicae, the causal agent of clubroot disease on Brassica spp. has been reported in Korea (2), but is not known to occur in China. In February of 2011, stunted and wilted shepherd's purse (SP) plants were observed in a field planted to oilseed rapes (B. napus) in Sichuan Province of China. Symptomatic SP plants also exhibited root galls. Disease incidence was 6.2% and 100% for SP and B. napus, respectively. Root galls on diseased SP plants were collected for pathogen identification. Many resting spores were observed when the root galls were examined under a light microscope. The resting spores were circular in shape, measuring 2.0 to 3.1 µm in diameter (average 2.6 µm). PCR amplification was conducted to confirm the pathogen. DNA was extracted from root galls and healthy roots (control) of SP. Two primers, TC2F (5'-AAACAACGAGTCAGCTTGAATGCTAGTGTG-3') and TC2R (5'-CTTTAGTTGTGTTTCGGCTAGGATGGTTCG-3') were used to detect P. brassicae (1). No PCR amplifications were observed with the control DNA as template. A fragment of the expected size (approximately 520 bp) was obtained when DNA was amplified from diseased roots of SP. These results suggest that the pathogen in the galled roots of SP is P. brassicae. Pathogenicity of P. brassicae in SP was tested on plants of both SP and Chinese cabbage (CC) (B. campestris ssp. pekinensis). A resting spore suspension prepared from naturally infected SP roots was mixed with a sterilized soil in two plastic pots, resulting in a final concentration of 5 × 106 spores/g soil. Soil treated with the same volume of sterile water was used as a control. Seeds of SP and CC were pre-germinated on moist filter paper for 2 days (20°C) and seeded into the infested and control pots, one seed per pot for planted for CC and four seeds per pot for SP. The pots were placed in a chamber at 15 to 25°C under 12 h light and 12 h dark. Plants in each pot were uprooted after 4 weeks and the roots of each plant were washed under tap water and rated for clubroot disease. No disease symptoms were observed in the control treatments of SP or CC. Plants of both species showed symptoms of clubroot, with the disease incidence of 62.5% and 100% on SP and CC, respectively. The pathogen was isolated from diseased roots of each plant and confirmed as P. brassicae based on morphological characteristics and PCR detection. To our knowledge, this is the first report of clubroot disease on C. bursa-pastoris in Sichuan Province of China. This finding suggests that it may be necessary to manage C. bursa-pastoris in cruciferous vegetable (cabbage, turnip) and oilseed rape production fields. References: (1) T. Cao et al. Plant Dis. 91:80, 2007. (2) W. G. Kim et al. Microbiology 39:233, 2011.

Coexistence of insulin-derived amyloidosis and an overlying acanthosis nigricans-like lesion at the site of insulin injection.

A 59-year-old patient with diabetes mellitus had been treated with human recombinant insulin for 4 years. He developed a solid mass on his left abdomen at the insulin injection site, which had an overlying pigmented verrucous plaque and keratinized papules, similar to acanthosis nigricans (AN). On histological examination, the mass was found to contain a deposit of amyloid in the dermis, with hyperkeratosis, papillomatosis and acanthosis in the epidermis. Using immunohistochemistry, the amyloid deposits were found to be positive for insulin. A few cases of localized insulin-derived amyloid deposits at injection sites have been reported previously, but none had significant epidermal changes. The coexistence of dermal insulin-derived amyloidosis and an overlying AN-like change, as found in our patient, has not been reported previously, to our knowledge. The presence of a tumour-like lesion at the injection site should be carefully examined, as injection of insulin into amyloid deposits can result in insulin resistance.

Beyond-limit light focusing in the intermediate zone.

We experimentally verify that a new nanolens of a designed plasmonic aperture can focus visible light to a single line with its width smaller than the limit of half the wavelength in the intermediate zone. The experimental measurement indicates that while the near field plays a role to increase the spot size in the near zone, it is negligible at the beyond-limit focused region; i.e., the focused light is dominated by the radiative fields. The image taken by the optical microscope shows that the fields focused have propagated to the far zone. Besides being of academic interest, the nanolens capable in achieving a lower diffraction limit in the intermediate zone is important for application possibilities.

Focusing of light beyond the diffraction limit of half the wavelength.

The diffraction limit sets the smallest achievable linewidth at half the wavelength. With a subwavelength plasmonic lens allowing one to reduce the diffraction via an asymmetry and to generate and squeeze the wave functions, an incident light is focused by the aperture to a single line with its width smaller than the limited value in the intermediate zone. The focused fields are capable of propagating in free space. This light focusing process, besides being of academic interest, is expected to open up a wide range of application possibilities.

Folliculotropic mycosis fungoides with eosinophilia and CD30+ large-cell transformation: a case with a fatal outcome presenting with multifocal lesions and leonine facies.

Eosinophilia is recognized as a poor prognostic factor in patients with cutaneous T-cell lymphoma (CTCL). We report a case of folliculotropic mycosis fungoides (FMF) presenting with multiple ulcerative nodular lesions and persistent eosinophilia. Severe facial lesions resulted in a leonine appearance. On histopathological examination, nodular infiltration of large CD30+ large cells was seen. When the previous biopsy specimens were reviewed, marked folliculotropism with atypical lymphocytes was identified in previous specimens 20 years before the blastic transformation. CC chemokine receptor 3 was expressed in tumour cells, whereas CXC chemokine receptor 3 was negative. Expression of interleukin (IL)-5 was detected in a few mononuclear lymphoid cells. This case demonstrates that T helper (Th)2-polarized tumour cells may produce Th2 cytokines including IL-5, which suggests that cytokines and chemokines may contribute to persistent eosinophilia and to recruitment of eosinophils into tumour lesions in advanced FMF.

Hypergammaglobulinaemic purpura associated with alcoholic liver cirrhosis.

Hypergammaglobulinaemic purpura (HP) is commonly found in Sjögren's syndrome. We report a rare association of HP arising in a patient with alcoholic liver cirrhosis. A 65-year-old man presented with palpable purpura on the legs. Histological examination of a biopsy taken from the purpura found leucocytoclastic vasculitis in the superficial and mid-dermis. The activity of the vasculitic skin lesions correlated with liver dysfunction. Increased IgA and IgG levels, and hypocomplementaemia, may account for the pathogenesis of the hypergammaglobulinaemic immune complex-mediated vasculitis in this case.

Persistent lymphoedema in Morbihan disease: formation of perilymphatic epithelioid cell granulomas as a possible pathogenesis.

Morbihan disease is a rare complication of rosacea, characterized by persistent lymphoedema on the upper half of the face, occurring during the chronic clinical course of rosacea. This refractory condition has been also designated as 'rosacea lymphoedema' and 'solid persistent facial oedema of rosacea'. We report a patient with Morbihan disease showing persistent lymphoedema on the upper half of the face accompanied by unique histological findings of striking dermal dilated lymphatics and damage of the lymphatics at the site of the adjacent epithelioid cell granulomas, with histiocytes bulging into the lymphatic lumen. The marked epithelioid cell granulomas forming around dermal lymphatic vessels with subsequent lymphatic damage and luminal obstruction by histiocytic infiltration may account for the development of lymphoedema in this patient.

Relativistic electromagnetic ion cyclotron instabilities.

The relativistic instabilities of electromagnetic ion cyclotron waves driven by MeV ions are analytically and numerically studied. As caused by wave magnetic field and in sharp contrast to the electrostatic case, interesting characteristics such as Alfve nic behavior and instability transition are discovered and illuminated in detail. The instabilities are reactive and are raised from the coupling of slow ions' first-order resonance and fast ions' second-order resonance, that is an essential extra mechanism due to relativistic effect. Because of the wave magnetic field, the nonresonant plasma dielectric is usually negative and large, that affects the instability conditions and scaling laws. A negative harmonic cyclotron frequency mismatch between the fast and slow ions is required for driving a cubic (and a coupled quadratic) instability; the cubic (square) root scaling of the peak growth rate makes the relativistic effect more important than classical mechanism, especially for low fast ion density and Lorentz factor being close to unity. For the cubic instability, there is a threshold (ceiling) on the slow ion temperature and density (the external magnetic field and the fast ion energy); the Alfve n velocity is required to be low. This Alfve nic behavior is interesting in physics and important for its applications. The case of fast protons in thermal deuterons is numerically studied and compared with the analytical results. When the slow ion temperature or density (the external magnetic field or the fast ion energy) is increased (reduced) to about twice (half) the threshold (ceiling), the same growth rate peak transits from the cubic instability to the coupled quadratic instability and a different cubic instability branch appears. The instability transition is an interesting new phenomenon for instability.

Cytosine arabinoside-induced vasculitis.

Dermatologic side effects of cytosine arabinoside (ara-C) are rare and most commonly occur after high-dose (more than 100 to 200 mg/m2 per day) therapy has been administered for several days. Although vascular reactions after combination chemotherapeutic regimens with ara-C have been anecdotally described, they have not been previously reported after single-agent chemotherapy with ara-C. Herein we describe two patients with acute nonlymphoblastic leukemia in whom cutaneous small vessel necrotizing vasculitis developed after high-dose single-agent chemotherapy with ara-C. Cutaneous lesions developed 3 to 5 days after initiation of therapy and resolved spontaneously within a week after the chemotherapeutic regimen was completed. No evidence of systemic vasculitis was present in either patient. Prior experimental data have demonstrated a direct toxic effect of ara-C on endothelial cells, and this outcome may represent the underlying mechanism of vascular injury.

Recurrent cutaneous necrotizing eosinophilic vasculitis. A novel eosinophil-mediated syndrome.

BACKGROUND AND DESIGN: Review of skin biopsy specimens showing necrotizing vasculitis revealed three patients with small dermal vessel eosinophilic vasculitis and common clinical features characterized by glucocorticoid responsive pruritic erythematous, purpuric papules and angioedema associated with peripheral blood eosinophilia. Indirect immunofluorescent localization of eosinophil granule proteins, neutrophil granule proteins, and mast cell tryptase, electron-microscopic evaluation and immunoperoxidase staining for vascular cell adhesion molecule type 1, intercellular adhesion molecule type I, endothelial-leukocyte adhesion molecule type 1, and very-late activation antigen type 4 were performed. Eosinophil-active cytokines in serum were evaluated by an eosinophil survival assay. OBSERVATIONS: Eight skin biopsy specimens from the three patients all showed small-vessel necrotizing vasculitis with exclusive eosinophil infiltration. Ultrastructural study demonstrated degenerating eosinophils and eosinophil granules in proximity to damaged endothelium. The affected small vessels showed marked deposition of the toxic eosinophil granule major basic protein in the vessel walls and expression of vascular cell adhesion molecule type 1 and intercellular adhesion molecule type 1 on the endothelium with adherence of very-late activation antigen type 4-positive eosinophils; E-selectin staining was negative. The presence of interleukin 5 in serum available from one patient was detected by an eosinophil survival assay. CONCLUSIONS: We studied three patients whose cutaneous lesions showed small-vessel eosinophilic vasculitis and who presented with recurrent glucocorticoid-responsive pruritic purpuric papules and angioedema. The presence of eosinophil-active cytokines in serum and the expression of vascular cell adhesion molecule type 1 on the endothelium of affected vessels may contribute to the selective adherence and localization of activate eosinophils. Subsequent release of cytotoxic proteins such as major basic protein may result in destruction of the endothelium in this unique syndrome.

Cutaneous polyarteritis nodosa: a clinical and histopathological study of 20 cases.

Twenty cases diagnosed as cutaneous polyarteritis nodosa (CPN) and confirmed by skin biopsy over the last 17 years were reviewed in our department. Based upon their clinical features, laboratory findings, and long-term observation of the disease course, they were divided into three groups. 1) Group 1 comprised 16 cases which were classified as the mild cutaneous form. The disease was confined to the skin with occasional involvement of peripheral nerves and skeletal muscles of the affected extremity. They generally followed a benign course. 2) Group 2 comprised 2 cases classified as the severe form. Despite severe clinical manifestations and several abnormal laboratory findings, the disease was limited to the skin, muscles, and peripheral nerves without any visceral involvement over follow-up periods of 11 years and 5 years, respectively. 3) Group 3 comprised 2 cases of the progressive form; in these the disease had begun with a cutaneous lesion and progressed to the systemic form after 19 and 18 year periods of recurrent episodes of cutaneous lesions, respectively. One died of gastrointestinal bleeding. In group 3, serum antinuclear antibodies and rheumatoid factor were positive. The autoimmune mechanism seems to play a role in this group. It is clear from the results of this study that not all patients whose vasculitic lesions are apparently limited to the skin remain in a benign course. Long-term follow-up is essential.

Churg-Strauss syndrome: report of a case without preexisting asthma.

A 38-year-old male with no history of asthma, who initially presented with episcleritis and subsequently developed symptoms of systemic vasculitis with marked blood eosinophilia, was diagnosed as having Churg-Strauss syndrome (CSS). Both the patient's skin lesions and pulmonary infiltrates revealed histologically proven vasculitis with predominantly eosinophilic infiltration. All the symptoms of systemic vasculitis except the persisting peripheral neuropathy dramatically improved after corticosteroid was systemically used. Since scattered non-asthmatic cases of CSS have been reported recently, and three such patients have died of acute heart failure due to delayed diagnosis, absence of asthma should not be regarded as an absolute criterion for exclusion of the diagnosis of CSS. Earlier recognition of this disease is important, since earlier institution of steroid therapy can prevent the acute onset of fatal cardiac involvement during the course of this disease.

Localized cyclotron mode driven by fast alpha particles under a nonuniform magnetic field.

Resonance requires precise synchronization. Surprisingly, relativistic cyclotron instability can survive under a magnetic field with its nonuniformity larger than the requirement of synchronism. Localized eigenmode observed in a hybrid simulation is found to be consistent with that predicted by an analytical theory including both profile and eigenvalue. Half of the spatial area of the wave profile is located where the frequency mismatch is negative as against to the positive requirement generally believed. The consequence on the alpha dynamics is also demonstrated.

Clinical and histopathological spectrum of cutaneous vasculitis in rheumatoid arthritis.

BACKGROUND: Cutaneous manifestations are the most frequent, and often the initial feature of extra-articular involvement in patients with rheumatoid vasculitis. OBJECTIVES: The purpose of the study was to evaluate the clinical and histological spectrum of cutaneous vasculitis and the associated systemic involvement in patients with rheumatoid vasculitis. METHODS: Among 525 patients with rheumatoid arthritis, 20 tissue specimens with histologically proven cutaneous necrotizing vasculitis from 11 patients were investigated by studying the types and levels of affected vessels and related clinical features. RESULTS: Small-vessel vasculitis identified as dermal necrotizing venulitis was found in 10 patients, clinically characterized by palpable purpura, maculopapular erythema, erythema elevatum diutinum and haemorrhagic blisters. Arteritis histologically resembling cutaneous polyarteritis nodosa, clinically characterized by subcutaneous nodules, livedo reticularis, atrophie blanche and deep ulcers was identified in four patients all with systemic complications. Coexistence of venulitis and arteritis was identified in three patients. Different cutaneous vasculitic manifestations often coexisted and recurred in the same patient. Three patients with systemic complications of mononeuritis multiplex (two of three), interstitial pulmonary fibrosis (two of three) and abdominal microaneurysms (one of three) died within 1 year of onset of the cutaneous vasculitis. Immunofluorescence demonstrated vessel wall deposition of IgM and/or complement in six of the seven patients examined. CONCLUSIONS: Features of cutaneous rheumatoid vasculitis overlapping both the characteristics of cutaneous necrotizing venulitis and cutaneous polyarteritis nodosa together with coexistence of these different type of vasculitis in the same or different lesional skin account for the associated diverse cutaneous vasculitic manifestations. Although dermal venulitis (leucocytoclastic vasculitis) was the most common presentation, the presence of leucocytoclastic vasculitis in rheumatoid patients did not necessarily indicate a favourable prognosis. Associations with mononeuritis multiplex and bowel involvement had a fatal prognosis, while patients with superficial dermal venulitis without other extra-articular involvement may follow a favourable prognosis.

Mucocutaneous manifestations in Japanese HIV-positive hemophiliacs.

BACKGROUND: Although various mucocutaneous manifestations have been reported in patients infected with HIV by sexual transmission or intravenous drug use, the prevalence and characteristics of skin disorders in HIV-positive hemophiliacs coinfected with hepatitis C virus (HCV) have rarely been described. OBJECTIVE: The purpose of this study was to clarify the characteristics of skin disorders in HIV-positive hemophiliacs and to identify differences in comparison with other HIV-positive groups. METHODS: A prospective study of the prevalence of mucocutaneous manifestations in 110 Japanese hemophiliacs (53 HIV-positive hemophiliacs including 24 AIDS and 57 HIV-negative hemophiliacs) was performed from July 1997 to July 1998. RESULT: None of the hemophiliacs developed Kaposi's sarcoma or sexually transmitted skin diseases. Eosinophilic folliculitis was observed in 3 AIDS patients. The incidence of folliculitis, common warts, seborrheic dermatitis, generalized eczema, oral candidiasis and herpes zoster was higher in HIV-positive than in HIV-negative hemophiliacs (p < 0.05). Although anti-HCV antibody was positive in all HIV-positive hemophiliacs, HCV-related dermatoses such as lichen planus and porphyria cutanea tarda were not observed. CONCLUSION: Although Kaposi's sarcoma and sexually transmitted skin diseases such as molluscum contagiosum, condyloma, and scabies are frequently associated with HIV, they were not found in the HIV-positive hemophiliacs in our study. HIV infection-related mucocutaneous manifestations are influenced not only by the presence of HIV but also by other factors such as the mode of transmission and sexual habit.

Granulomatous mycosis fungoides with small intestinal involvement and a fatal outcome.

We report a case of granulomatous mycosis fungoides that progressed into fatal gastrointestinal involvement 4 years after the onset of skin lesions, despite improvement of the skin lesions in response to a combination of PUVA and systemic interferon-gamma therapy. Histological examination showed Pautrier's microabscesses with granuloma annulare-like features and sarcoidal granuloma formation in the plaque stage, proliferation of blast-transformed atypical lymphocytes with persistent granuloma formation in the tumour stage, and metastatic lesions. A literature review of granulomatous mycosis fungoides revealed that 11 of the 24 reported cases died of the disease, and like our case, seven died within 5 years. We suggest that mycosis fungoides with granulomatous reactions does not indicate a favourable prognosis.

Cutaneous vasculitis in Behçet's disease: a clinical and histopathologic study of 20 patients.

BACKGROUND: Despite the frequency of small vessel vasculitis in skin lesions of Behçet's disease (BD), BD is classified as a neutrophilic dermatosis. OBJECTIVE: Our goal was to determine whether the various cutaneous manifestations of BD are secondary to cutaneous vasculitis. METHODS: Twenty-three specimens with histologically proven necrotizing vasculitis from 20 of 42 patients with BD were investigated. RESULTS: The cutaneous vasculitic manifestations were characterized as erythema nodosum-like eruptions, palpable purpura, hemorrhagic blisters, infiltrated erythema, Sweet's syndrome-like eruptions, papulopustular lesions, and extragenital ulcerations. Combinations of various skin lesions were commonly seen in the same patient. Venous vessels in the entire dermis to the subcutis were affected with sparing of arterial vessels from middermis to subcutis. Histologic features included leukocytoclastic vasculitis in seven and lymphocytic vasculitis in 13 patients with extensive to focal localized fibrinoid necrosis of vessel walls. CONCLUSION: Cutaneous vasculitis in BD is predominantly venulitis or phlebitis. Approximately half (48%; 20 of 42) of BD patients with cutaneous lesions had either lymphocytic (31%; 13 of 42) or leukocytoclastic vasculitis (17%; 7 of 42). We suggest that BD be considered as a vasculitis-associated disease separate from the neutrophilic dermatoses.

Cefotiam-induced contact urticaria syndrome: an occupational condition in Japanese nurses.

A case of occupational contact urticaria syndrome caused by cefotiam dihydrochloride (CTM) in a Japanese nurse is reported. The patient had become sensitized to CTM through the process of preparing antibiotics 8 months before she developed symptoms. A review of the literature revealed 13 similar cases, all involving Japanese nurses, reported since CTM became available in Japan.