Clinical And Myopathological Features Of Dermatomyositis And The Pathological Study Of Plasmacytoid Dendritic Cells In Muscle Tissue Of Dermatomyositis

PartⅠClinical and myopathological analysis of 34 cases with dermatomyositisBACKGROUND:Dermatomyositis is a systemic inflammatory disease involves both skeletal muscles and skin subsequently or simultaneously, which can onset in any age and shows higher incidence in females. According to clinical features, Dalakas divided dermatomyositis into three subgroups:①Most cases show progressive muscle weakness and typical skin lesion, which are called myopathic dermatomyositis (MDM);②Part of cases lack symptoms and pathological changes of inflammatory myopathies but show typical skin lesion, which are called dermatomyositis sine myositis (DSM);③A few patients complaints muscle weakness and typical perifascicular atrophy can be seen by muscle biopsy, but there are no skin lesions. It is called dermatomyositis sine dermatitis (DSD). DSD is easily misdiagnosed as polymyositis, so muscle biopsy is necessary. Typical myopathological changes of dermatomyositis include perifascicular atrophy, perivascular inflammation, but clinical features need to be considered when referring to some cases with untypical or mild pathological changes. This part aims to summerize the relationship between clinical features and pathological changes in cases with dermatomyositis (including MDM, DSM and DSD).OBJECTIVE:By retrospectively analyzing the clinical datas of 34 cases with dermatomyositis diagnosed by muscle biopsy during these 4 years and summerizing muscular pathological features of dermatomyositis, to learn about the relationship between clinical features and pathological changes in cases with dermatomyositis and to make clinical subgroups of dermatomyositis better known by clinicians.METHOD:34 patients diagnosed with dermatomyositis by muscle biopsy in the Laboratory of Neuromuscular Disorders and Department of Neurology of Qilu Hospital from Auguest 2005 to December 2009 were analysed retrospectively. We summerized clinical features and muscular pathological changes of these cases. HE, MGT, NADH. SDH, COX, SDH/COX, PAS and ORO staining were carried out in all muscle samples. Immunohistochemical stainings were performed in six samples with petivasculitis with anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD45RA and anti-CD45RO antibody.RESULT:There were 10 males and 24 females, sex ratio of male to female is 1:2.4. The mean age of onset was 40±20.2 years, ranging from 6 to 72 years. The mean course was 6.3±8.6 months, ranging from 1-36 months.28 cases had skin lesions,30 cases had obvious proximal muscle weakness and 16 cases had myalgia or arthralgia. 8 cases had a fever at the same time of onset. The serum creatine kinase level raise in 26 cases of 31. Serum rheumatic marker of 11 patients were tested, and only 7 patients had positive ANA. EMG was performed in 16 cases, of which 12 cases showed myogenic changes,3 showed neurogenic changes and 1 case showed mixed changes. As for muscle pathology,25 cases showed typical perifascicular atrophy, companied by significant proliferation of perimysium. Generally, the fibers of the regions of perifascicular atrophy are basophilla, and the enzyme activity of NADH and SDH are increased, the enzyme activity of COX are decreased.3 cases had blue fibers in SDH/COX dual-staining. The glycogen are increased in the fibers of the regions of perifascicular atrophy in 11 cases and decreased in 9 cases.5 cases showed untypical perifascicular atrophy, but small groups necrotic and regenerative fibers could be seen in peri-fascicle. Punched-out fibers could be seen in peri-fascicle of 14 cases.12 cases showed dialated capillaries in peri-fascicle. Fibrinoid necrosis of three arteriolas in one case can be seen.17 cases showed perivasculitis, which mainly were CD4+T lymphocytes and B lymphocytes. In 6 cases, inflammatory cells localized in endomysium.4 cases were normal or showed mild changes by muscle biopsy. According to clinical manifestation and the features of muscle pathology,25 cases are diagnosed with MDM,4 cases are DSM and 6 cases are DSD.CONCLUSION:1. Skin lesions and proximal muscle weakness are typical clinical manifestations of dermatomyositis. According to different clinical features, dermatomyositis can be divided into MDM, DSM and DSD. Serum creatine kinase levels and EMG test are of great help. Muscle pathology is used to make the diagnosis.2. Most DM show typical perifascicular atrophy and are easy to be diagnosed. As for a few cases with untypical perifascicular atrophy, small groups necrotic and regenerative fibers in peri-fascicle and typical skin lesion lead to definite diagnosis. Because of normal or mild changes of muscle pathology, clinical manifestations should be serious considered when make a diagnosis of DSM. 3. The features of histochemical and enzyme histochemistry staining in muscle fibers with perifascicular atrophy of MDM are unique and reveals metobalic abnormality and mitochondrial dysfunction in this regions. Muscle fibers in the central of muscle bundle can be involved in some.serious cases.PartⅡThe pathological study of plasmacytoid dendritic cells in muscle tissue of DermatomyositisBACKGROUND:Dermatomyositis is a systemic inflammatory disease involves both skeletal muscles and skin subsequently or simultaneously. Many researches believe antibodies and complements mediated by CD4+T lymphocytes and B cells dispose in the wall of capillary muscle tissue, which lead to sternosis or blockage of vessels and further the formation of perifascicular and focal loss of muscle fibers. However, there are still two problems:①The target antigen in the wall of capillary has not been found.②Animal model with ischemic myopathy manifests muscle fibers in the central of muscle bundle are more fragile to ischemia than those in peri-fascicle. So this theory cannot explain the pathogenesis of dermatomyositis perfectly. Lately, some studies abroad find that plasmacytoid dendritic cells (pDC) infiltration and possible relationship between interferon-Ⅰproduced by pDCs and pathogenesis of dermatomyositis. But there are no related reports in our China. Our research discovers obvious perivascular pDCs infiltration in biopsied muscle tissues especially in the region of perivasculitis of perimysium. Also we discuss the pathological meaning according to the function and distribution of pDCsOBJECTIVE:To study the morphology and distribution of pDCs in muscle tissues of dermatomyositis and to explore the pathological meaning according to the function and distribution of pDCs.METHOD:HE staining and immunohistochemical staining with anti-CD68 and anti-CD303 antibodies were performed in 30 biopsied muscle tissues of dermatomyositis.25 cases of polymyositis which muscle pathologies showed obvious focal inflammatory infiltration were selected as controls.RESULT:Perivasculitis in perimysium could be seen in 17 of 30 cases with dermatomyositis and focal inflammatory infiltration in endomysium in 6 cases Using immunohistochemistry study,19 cases from DM were infiltrated by macrophages which are CD68 positive and CD303 negative,20 cases with DM were infiltrated by pDC which are CD303 positive. The location of pDC are:perivascular of interfascicular septae only (15/20); endomysium only (3/20) and both (2/20). Myopathic changes such as necrotic and regenerating fibers and inflammatory infiltration could be seen in PM. There is no or a few scattered pDCs infiltration in PMCONCLUSION:There is no or a few scattered pDCs infiltration in muscle tissues of polymyositis and many pDC infiltration in muscle tissues of dermatomyositis, which mainly infiltrated the wide interfascicular septae and may have connection with the formation of perifascicular atrophy and play a roll in the pathogenesis of dermatomy o sitis.