Clinical And Pathological Analysis Of The Idiopathic Inflammatory Myopathies

Objective：Idiopathic inflammatory myopathies (IIMs) are considered tobe a group of acquired autoimmune disease affecting the skeletal muscle.Inflammatory cells infiltration is one of the important features of IIMs. Thesediseases include polymyositis (PM), dermatomyositis (DM), sporadicinclusion-body myositis (sIBM), nonspeific myositis (NSM) andimmune-mediated necrotizing myopathy (IMNM).Anti-signal recognition particle associated with necrotizing myopathy（ASANM）belongs to one of the major subtypes of IMNM. The clinicalmanifestations, laboratory examination and electromyography (EMG) ofASANM are similar to PM, but its illness is more serious and resistant toglucocorticoid treatment. Routine histopathological examination showedextensive necrosis and regeneration of muscle fibers, interstitial hyperplasiaand with no or less inflammatory cells infiltration. Anti-signal recognitionparticle (SRP) autoantibodies are myositis-specific antibodies (MSAs), whichplays an important role in diagnosis which is presented mainly in thecytoplasm of the necrosis or degeneration muscle fiber.Due to similarities in the clinical manifestations and routinehistopathological examination of the various subtypes among IIMs, simplyrelying on the clinical manifestations and routine histopathologicalexamination is highly prone to misdiagnosis and resultant delay in applyingthe appropriate treatment.In this study, muscle routine histological staining and immuno-histochemical methods is employed to detect patient muscle samples,including the degree and the subset of cell infiltration and the expression ofanti-SRP autoantibody, and summarize the clinical and pathological features toidentify the common type of IIMs. This forms the clinical and pathological theoretical basis for more accurate differentiation and diagnosis, and plays animportant role in determining the treatment and the prognosis of the disease.Methods: The study is divided into two groups-the experimental groupand the control group. The experimental group consists of27patientsclinically diagnosed with idiopathic inflammatory myopathy, each withcomplete clinical and pathological data. This includes12cases of PM and12cases of DM based on the Bohan and Peter diagnosis criteria or Dalakasdiagnosis criteria, and3cases of IBM based on the Griggs diagnosis criteria.The control group consists of8patients with pathological diagnosis of normalpatients.The following was examined for each patient: age of onset, sex, duration,family history and personal history, location and degree of muscle weakness,whether accompanied with rash, muscle atrophy parts, whether accompaniedwith other diseases, visceral involvement, serum muscle enzymes values,immunological parameters, the results of the EMG and ECG. Musclebiopsies were done for staining, including HE staining, MGT staining,NADH-TR staining, ACP staining, SDH staining, NSE staining, ATPasestaining (PH4.5and PH10.2), PAS staining, ORO staining, to observe themorphological changes; With anti CD3, CD4, CD8, CD19, CD20, CD68protein monoclonal antibodies and SRP protein polyclonal antibody doimmunohistochemical staining (IHC).Results:1The clinical characteristics of IIMThis study collected27cases which have a diagnosis of idiopathicinflammatory myopathy from August2010to January2014in our hospital,including12cases with PM,12cases with DM and3cases with IBM. Fromthis datas we can see that PM and DM have a high incidence in our area,accounting for88.89%of the total and IBM is rare, accounting for11.11%ofthe total.Both in PM and DM, the male and female incidence ratio is1:2, morecommon in women. The onset of disease is mostly subcute or chronic. Theonset age in PM patients presents two incidence peaks:20-30years old (five cases,41.67%) and45-55years old (3cases,25%). The age of onset in DMpatients is60-70years old (8cases,66.67%). In this study, there are only threeIBM patients:2males and1female. The age of onset in2cases is24yearsold, and the other is41years old. The3cases are mostly chronic processes.The main clinical characteristics of IIMs are weakness, muscle pain. It may beaccompanied by muscle atrophy, dysphagia and dyspnea. Most DM patientshave typical rash: heliotrope (purple) periorbital oedema, violaceous papules(Gottron’s papules) or macules (Gottron’s sign), scaly if chronic, atmetacarpophalyngeal and interphalyngeal joints and other bony prominences;erythema of chest and neck (V-sign) and upper back (shawl sign). IIMs areoften accompanied with heart and lung disease. The thyroid disorders, cancerand other connective tissue diseases may be found in IIMs. Laboratoryexamination showed the elevated serum creatine kinase level in most patients.The high values of MYO, ALT, AST, and LDH in different degrees also can beseen in IIMs. The EMGs showed myogenic abnormality in25cases (92.59%).2The pathological characteristics of IIMs:2.1Routine histological stainingIn the light microscope, except for one IBM case, the muscle specimensof all cases observed inflammatory cell infiltrate in different degrees. Theinflammatory cell infiltrate is more scattered and surrounding the necroticmuscle fibers in PM. The interstitial inflammatory cell infiltration andinflammatory cell also could be seen in PM. DM patients with inflammatorycells were located in the perimysium region and surrounding the blood vessels.20cases showed obvious muscle fiber degeneration, necrosis andphagocytosis;17cases have been seen the gap widened;9cases of obviousperimysium atrophy, and all of them belong to DM;3cases of rimmedvacuole, all of them are part of IBM;13cases of inflammatory cell invadingthe non-necrotic muscle fibers, which includes10cases in PM,3cases in DM;20cases of obvious muscle atrophy, mainly in round appearance, whichincludes8cases in PM,9cases in DM,3cases in IBM;2cases of DMpatients also can be seen small blood vessels proliferation；in addition, some patients presented varying degrees of muscle regeneration, muscle splitting,the nucleus shift and hypertrophy of muscle fibers.27cases showed Oxidasedistribution and muscle fiber structure damage. Except for one IBM case, themuscle specimens of all cases showed some atrophic or necrotic muscle fibersstained with NSE staining.15patients showed varying degrees of increasedfat content in ORO staining.15cases of PAS staining showed slightly elevatedglycogen ingredients.25cases of ATP staining showed of two types of musclefibers distribution normal persons, two cases have the advantage of the type Imuscle fibers, six cases of type II muscle fibers advantage I muscle fiberspredominate in2patients, one case of DM, one case of IBM. One IBM casecan be seen atypical ragged red fibers (RRF) with MGT staining.2.2Immunohistochemical stainingThe main subsets of inflammatory cell in PM and IBM are CD3, CD8,CD68positive cells; and in DM are CD3, CD4, CD20, CD68positive cells. Inthe control group, no patient showed positive staining with IHC. IHC ofAnti-SRP antibodies showed no positive staining.Conclusions:1PM and DM is common in our region, but the clinical manifestation issimilar, complex and diverse. Therefore, the disease is easily misdiagnosedand missed.So if we suspect it is IIMs, we should do pathlogical examinationto differentiate diagnosis.2The main subsets of inflammatory cell in PM and IBM are CD3, CD8, CD68positive cells, indicates that cytotoxic T cells and macrophagesare given priority to, prompting the cellular immunity plays an important rolein PM and IBM; and in DM are CD3, CD4, CD20, CD68positive cells，indicates that helper T cells, B cells and macrophages are given priority to,prompting the humoral immune plays an important role in DM. IHC of CD3, CD19antibody has no obvious significance in differential diagnosis.3In recent years, ASANM is rare.