Microvascular changes in early and advanced dermatomyositis: a quantitative study

In adult dermatomyositis 10 muscle specimens with no or minimal histological alterations were compared with 7 that showed typical alterations. Five specimens from patients with inclusion body myositis, 5 from patients with polymyositis, and 8 from normal subjects served as controls. Vascular endothelium, visualized with the lectin Ulex europaeus agglutinin I, and complement membrane attack complex were demonstrated in the same cryostat sections by paired immunofluorescence. Large randomly selected fields were analyzed to determine the number of capillaries per square millimeter of fiber area (capillary density), per 1,000-microns 2 area of each muscle fiber (capillary index), and in 100 x 100-microns grid squares. In dermatomyositis specimens with minimal structural alterations there was focal capillary depletion, the capillary density was significantly reduced, and the frequency distributions of the capillary index and grid count were shifted to the left. In advanced dermatomyositis specimens, the findings were similar but more severe. In both kinds of specimens, clusters of capillaries reacted for complement membrane attack complex. The 2 patients with the highest proportion of vessels positive for membrane attack complex had a fulminant and fatal course. In polymyositis and inclusion body myositis specimens, the capillaries had a normal overall density and none reacted for membrane attack complex. The findings imply that the capillaries are an early and specific target of the disease process in dermatomyositis.     

Streptococcal myositis as a complication of juvenile dermatomyositis

The infection of muscle is an infrequent condition. We report on a patient with a juvenile form of dermatomyositis who developed infectious myositis caused by Streptococcus pyogenes. The inflammatory myopathy probably favoured the colonization of muscle during a bacteremia related to the skin lesions. The main forms of streptococcal myositis, which can currently be differentiated by means of imaging techniques, are discussed in addition to its treatment and prognosis.     

青少年型皮肌炎的病理特点(附6例报告)

目的 探讨青少年型皮肌炎的皮肤和骨骼肌微血管病理改变规律。方法 6例患儿的发病年龄在7～14岁之间，主要表现为急性或亚急性起病的四肢肌肉无力，伴随面部和颈部皮肤水纹样皮疹。对所有患者的肌肉进行活检，其中2例患者进行皮肤活检，肌肉标本进行常规组织学和酶组织化学染色，皮肤和肌肉标本进行电镜检查。结果 6例患者均存在典型皮肌炎的肌肉病理改变特点，表现为以肌束衣为主的炎细胞浸润和束周分布的肌纤维空泡变性和再生现象。非特异性酯酶染色显示小血管和毛细血管内皮细胞深染。电镜检查发现皮肤毛细血管内皮细胞坏死消失后残留的基底膜结构和细胞降解产物，在部分成熟毛细血管内皮细胞的胞浆内可见管网包涵体，该包涵体不出现在小血管坏死和再生的内皮细胞以及平滑肌细胞内。相同改变规律的微血管病变也出现在骨骼肌内。结论 皮肤具有和骨骼肌相同的微血管病理改变规律。内皮细胞损伤是青少年型皮肌炎微血管病的主要病理改变。显然青少年型皮肌炎是血管内皮细胞病。束周肌纤维病变为继发于微血管内皮细胞病变的缺血性损伤。     

Aerobic training in persons who have recovered from juvenile dermatomyositis

A recent study has shown that 36 persons who had recovered from juvenile dermatomyositis (JDM) have on average an 18% decrease in maximal oxygen uptake. The objective of this study was to investigate the effect of a 12-week aerobic training program in this group, and assess whether aerobic training can normalize aerobic capacity to the expected level for age and gender.The patients participating in the study, one male and nine females (16–42 years of age), were in remission from JDM, defined as no clinical or biochemical evidence of disease activity and no medical treatment for 1 year. The patients had a median disease duration of 3.4 years (1.4–10.3), a median treatment duration of 2.4 years (0.4–9.3) and a median duration of remission of 7.0 years (1.2–30.0).Patients trained at home on a cycle ergometer for 12 weeks at a heart rate interval corresponding to 65% of their maximal oxygen uptake (VO_2max)_. VO_2max and maximal workload (W_max) were determined before and after the 12-week training period through an incremental cycling test to exhaustion. The patients served as their own controls.Eight patients with JDM in remission completed the 12-week exercise program; one patient completed 9 weeks out of the 12-week program and one dropped out of the study. Training increased VO_2max and W_max by 26% and 30% (P < 0.001). Creatine kinase (CK) levels were normal pre-training and did not change with training, reflecting no muscle damage. We also found that at a given workload, heart rate was lowered significantly after the 12-week training period, indicating an improvement in cardiovascular fitness.This study shows that 12 weeks of moderate-intensity aerobic training is an effective and safe method to increase oxidative capacity and fitness in persons who have recovered from JDM. The results indicate that the low oxidative capacity in JDM patients in remission is reversible and can be improved. Thus, we recommend frequent aerobic training to be incorporated into supervised physiotherapy sessions in the treatment of JDM patients in remission.     

Quantitative muscle ultrasonography in the follow‐up of juvenile dermatomyositis

Introduction: We explored the use of quantitative muscle ultrasonography (QMUS) for follow‐up of juvenile dermatomyositis (JDM). Methods: Seven JDM patients were evaluated at diagnosis and 1, 3, 6, 12, and 24 months using the Childhood Myositis Assessment Scale (CMAS) and QMUS. Muscle thickness (MT) and quantitative muscle echo intensity (EI) were assessed with QMUS in 4 muscles. Results: Six patients experienced a monocyclic course. At diagnosis EI was slightly increased, and MT was relatively normal. After start of treatment MT first decreased and EI increased, with normalization of EI within 6–12 months (n = 4). One patient had higher EIs at diagnosis and slower normalization, indicating fibrosis, despite early normalization of CMAS. One patient experienced a chronic course, with high EIs and atrophy during follow‐up. Conclusions: QMUS can provide additional information for follow‐up of JDM regarding disease severity and residual muscle damage, particularly after normalization of CMAS. Muscle Nerve 52: 540–546, 2015     

Near‐infrared spectroscopy during exercise and recovery in children with juvenile dermatomyositis

Introduction: We hypothesized that microvascular disturbances in muscle tissue play a role in the reduced exercise capacity in juvenile dermatomyositis (JDM). Methods: Children with JDM, children with juvenile idiopathic arthritis (clinical controls), and healthy children performed a maximal incremental cycloergometric test from which normalized concentration changes in oxygenated hemoglobin (Δ[O₂Hb]) and total hemoglobin (Δ[tHb]) as well as the half‐recovery times of both signals were determined from the vastus medialis and vastus lateralis muscles using near‐infrared spectroscopy. Results: Children with JDM had lower Δ[tHb] values in the vastus medialis at work rates of 25%, 50%, 75%, and 100% of maximal compared with healthy children; the increase in Δ[tHb] with increasing intensity seen in healthy children was absent in children with JDM. Other outcome measures did not differ by group. Conclusions: The results suggest that children with JDM may experience difficulties in increasing muscle blood volume with more strenuous exercise. Muscle Nerve, 2013     

Basal ganglia mass lesions in juvenile rheumatoid arthritis

A 2-year-old boy suffered aphasia, hypotonia, dystonia, and loss of activity and spontaneous speech during an active stage of juvenile rheumatoid arthritis with pericarditis, fever, anemia, and a high antinuclear antibody titer. These neurologic signs slowly improved with corticosteroid treatment but fluctuated over 1 year. The neuroimaging studies revealed irregular mass lesions in the basal ganglia bilaterally mainly involving the globus pallidus. They gradually decreased in size and almost disappeared after 1 year. A stereotactic brain biopsy revealed a slight proliferation of astrocytes. Chorioretinitis was also observed during the clinical course. A chronic inflammatory process involving cerebral vessels was suspected, although angiography did not demonstrate cerebral vasculitis. The possibility of central nervous system lymphoma could not be eliminated. The type of aphasia and the relation to the lesion sites are discussed.     

血管损伤修复与基质金属蛋白酶★

背景：基质金属蛋白酶是一组能特异降解细胞外基质成分依赖锌的酶家族，近年来研究发现其参与了血管损伤后早期应激反应，与血管损伤后再狭窄发生相关。 目的：就基质金属蛋白酶在血管损伤中的一些生理病理过程做一综述。 方法：应用计算机检索Medline数据库、Ovid数据库、Springerlink数据库、维普数据库及中国知网数据库，纳入1990/2010发表的29篇基质金属蛋白酶与血管损伤以及药物等干预有关的文献进行总结分析。 结果与结论：心血管动脉系统在损伤后，包括经皮腔内血管成形后血管狭窄的发生率较高。基质金属蛋白酶在受损动脉的局部表达增加，通过促进内膜增厚和改变血管重构而促进血管损伤后再狭窄的发生。因此，降低血管受损局部基质金属蛋白酶表达将成为防治血管内再狭窄的一个方向。 关键词：血管损伤；血管内再狭窄；基质金属蛋白酶；基质金属蛋白酶组织抑制因子；血管组织工程     

Metalloproteases and intracranial vascular lesions.

Recent studies have suggested that metalloproteinases (MMP) might be involved in the pathogenesis of cerebral aneurysm formation and rupture and that elevated serum levels of MMP may effectively be considered as possible markers of cerebrovascular malformations. The present study was planned in order to verify if serum levels of MMPs may be the mirror of the MMP activity in the wall of intracranial aneurysms, reflecting the predisposition to aneurysm development and/or rupture. A series of 84 patients operated for intracranial cerebrovascular lesions (63 aneurysms and 21 arterovenous malformations (AVM)) and 20 controls entered the study. Among the 63 cases of intracranial aneurysms, nine were discovered before rupture, while 54 patients were included after subarachnoid hemorrhage (SAH). Using radioimmunoassay, plasma elastase levels were measured in all cases, while in 25 cases, when aneurysmectomy was possible, the activity of elastase and collagenase were measured in aneurysm samples. Mean plasma elastase level in patients bearing both an intracranial aneurysm or an intracranial AVM was significantly higher than in controls, while there was no significant difference between plasmatic level of elastase in patients with aneurysms when compared with patients bearing an intracranial AVM; there was no significant difference between mean elastase level in patients who suffered SAH and patients bearing an intracranial unruptured aneurysm. The activity of elastase and collagenase measured in the aneurysm wall were significantly higher in cases of ruptured than in unruptured aneurysms. The present results show that plasmatic level of elastase does not reflect the activity of MMP as measured in the aneurysm wall and that the patterns of MMP activities measured in the aneurysm wall differ considerably at different stages of SAH. This suggests that local rather than systemic changes in metalloproteases activity might be involved in cerebral aneurysm formation and rupture.     

Fundamental pathological lesions in vascular dementia

This review concerns the fundamental cerebral lesions in cases of vascular dementia. Extracerebral vascular alterations are dominated by atherosclerosis with or without thrombosis. In addition, occlusion of extracerebral arteries can be induced by thrombo-embolism and in rare cases by other vascular diseases, chiefly arteritis. Intracerebral microangiopathies are usually of arteriolosclerotic or hyalinotic types in which there is degeneration of smooth muscle cells of the media and deposition of components of extracellular matrix, chiefly collagens. Ageing, chronic hypertension, hyperlipidemias and diabetes are important factors inducing vascular lesions. The vascular lesions, often combined with systemic factors, may produce various ischemic and edematous alterations of the brain parenchyma. Occlusion and obliteration of arteries (macroangiopathy) are associated with large infarcts, whereas microangiopathy may cause lacunar infarcts and some forms of white matter degeneration. Cases of vascular dementia usually present many types of lesions in the brain parenchyma and its arterial supply. The extent and location of the injuries differ considerably from case to case. Location o(f the lesions, volume of destroyed tissue, multiplicity and bilateral occurrence are most important parameters underlying the clinical manifestations in vascular dementia. A strategic location of a small injury is in some cases of particular importance.     

A rare complication of generalized edema in juvenile dermatomyositis: a report of one case

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by inflammation of the muscle, connective tissue, skin, gastrointestinal tract and small nerves. Periorbital and facial edema may also be associated. Although localized edema is a common feature of juvenile dermatomyositis, generalized edema has been reported rarely. In this article, we report a 14-year-old boy with juvenile dermatomyositis presenting with generalized edema. Of the diagnostic criteria of JDM, severe symmetric weakness of the proximal musculature, characteristic cutaneous changes, elevated serum muscle enzymes and myopathic electromyographic abnormalities were observed. Magnetic resonance imaging (MRI) of the lower extremities and pelvis showed marked diffuse edema in the subcutaneous tissue, muscles and myofascia. We suggest that MRI findings, which are not among the diagnostic criteria, may also be included in the diagnostic criteria of JDM. To the best of our knowledge, this is the 19th case of JDM reported for generalized edema in the English literature.     

Nature of the mononuclear infiltrate and the mechanism of muscle damage in juvenile dermatomyositis and Duchenne muscular dystrophy

Normal skeletal muscle does not express class I MHC antigens. In contrast, these antigens are strongly expressed at the periphery of muscle fibres in patients with juvenile dermatomyositis (JDM) and Duchenne muscular dystrophy (DMD). Interferons can induce the expression of class I antigens, but in this study interferon-gamma could not be detected in JDM muscle biopsy specimens using four different immunocytochemical techniques. However, an infiltrate of mononuclear cells capable of synthesising interferons was present in biopsies from JDM and DMD patients. The predominant cell types detected in both diseases were macrophages and T lymphocytes, these two cell types comprising more than 80% of the infiltrating mononuclear cells. A striking predominance of CD4+ helper/inducer T cells was observed. The majority of these cells expressed class II MHC antigens and were, therefore, considered to be activated. Additional evidence for the functional activity of CD4+ T cells was derived from the finding that it was this population of cells from JDM biopsies which proliferated in response to interleukin-2 in vitro. T cell subsets in peripheral blood were also investigated in JDM and DMD patients. Only in the case of JDM were any significant differences from normal observed, where a significant reduction in the number of peripheral blood CD8+ T cells resulted in an elevation of CD4+/CD/8+ ratios. The role of CD4+ T cells and aberrant class I MHC antigen expression in mediating muscle damage in JDM and DMD is discussed.     

Focal lesions of muscle in peripheral vascular disease

Summary Lesions in skeletal muscle resulting from ischemia caused by peripheral vascular disease in two patients were essentially identical to the early muscle lesions of Duchenne muscular dystrophy (DMD) patients and carriers of that disease, as well as to the early muscle lesions of experimental animals with aorta ligations plus a small dose of 5-hydroxytryptamine (serotonin). The one similarity is harmonious with, although does not necessarily advance, the ischemia hypothesis of DMD, and the other supports the ischemia mechanism proposed in the animal model.

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Zusammenfassung Es werden Veränderungen am Skeletmuskel bei zwei Patienten mit peripheren Gefäßerkrankungen beschrieben. Diese sind im wesentlichen identisch mit den frühen histologischen Veränderungen bei Duchenne'scher Dystrophie sowie bei Konduktorinnen dieser Krankheit und ebenfalls gleichartig mit denjenigen, die experimentell durch Ligatur der Aorta und zusätzlich kleinen Dosen von Serotonin am Versuchstier bewirkt werden können. Die erstgenannte Ähnlichkeit its vereinbar — obwohl nicht notwendigerweise beweisend — mit der Ischämietheorie der progressiven Muskeldystrophie. Die zweitgenannte Ähnlichkeit stützt die Annahme eines ischämischen Mechanismus, wie er für die Ergebnisse des Tierversuches vorgeschlagen wurde.

     

Atypical focal MRI lesions in a case of juvenile Alexander's disease

We present a juvenile case of Alexander's disease with atypical focal magnetic resonance imaging-detected lesions and elevated levels of lactate in cerebrospinal fluid. The diagnosis was based on the neuropathological finding of a diffuse accumulation of Rosenthal fibers within the brain and the spinal cord. The diagnosis was confirmed by detection of a mutation in exon 1 at nucleotide position 249 of glial fibrillary acidic protein cDNA, a finding previously reported in cases of infantile Alexander's disease.     

Podoplanin expression in advanced atherosclerotic lesions of human aortas

Thrombus formation on disrupted atherosclerotic lesion is a key mechanism of cardiovascular events. Podoplanin (Aggrus), expressed on the surface of several tumor cells, is an endogenous ligand for C-type lectin-like receptor 2 (CLEC-2), and is involved in tumor cell-induced platelet aggregation and its malignant potency. Podoplanin, which is also expressed in lymphatic endothelial cells, facilitates blood/lymphatic vessel separation. However, podoplanin expression in atherosclerotic lesion has not been investigated. To clarify podoplanin expression in atherosclerotic lesion and to assess its importance for the onset of cardiovascular events, we examined podoplanin expression in abdominal aortas obtained from 31 autopsy cases. Immunohistochemical analysis indicated that podoplanin was localized to smooth muscle cells and macrophages. Moreover, podoplanin immunoreactivity was increased in advanced atherosclerotic lesions containing necrotic core, many macrophages and smooth muscle cells, compared with early lesions composed of smooth muscle cells and small numbers of macrophages. Furthermore, Western-blot and real time-PCR analyses showed that podoplanin expression was significantly enhanced in advanced atherosclerotic lesions, compared with early lesions. These results suggest that podoplanin contributes to thrombotic property of advanced stages of atherosclerosis and that it might be a novel molecular target for an anti-thrombus drug.