肌炎的临床诊断

↑↑↑
IBM >50 M Rare No Yes P=D No Normal or ↑
Adaptive immune system
B cells Subgrouping according to autoantibody profile seems to be a way to understand molecular pathways and predict treatment response
病理：肌肉的坏死是其突出临床 表现,炎性浸润可以很轻或不明显
预后因病因不同而不同
坏死性肌炎(NM)
自身免疫性坏死性肌病
① 抗SRP相关 ② 抗HMGCR相关 ③ 无自身抗体存在
药物相关坏死性肌病 肿瘤相关坏死性肌病
坏死性肌炎(NM)
坏死性肌炎(NM)
坏死性肌炎(NM)
IIM: CLINICAL FEADTMURES PM
PM: IMMUNOPATHOGENESIS
Immunopathology
CD8+ cytotoxic memory T cells invade nonnecrotic muscle fibers
MHC class I expression
a/b-T cells, oligoclonal TCR gene rearrangements antigen-driven response
Age at onset:
Adult, child Adult
Sex preference:
F
F
Family history:
No
No
Association with malignancy: Yes
Slight
CTD:
Yes
Yes
Weakness:
P>D
P>D
Rash:
Yes
No
CK:
↑↑↑, nl
Lymph
T B nodes
B B
T
T BT
APCs
Anti-Jo-1 T
IL-1a
Virus
T
T cell
B
B cell
Plasmacytoid DC
Inflammatory cell
T
Histidyl-tRNA synthetase T
Muscle fiber
Regenerating muscle fiber expressing histidyl-tRNA synthetase
Macrophages
Dendritic cells
Page G et al A&R 50: 199, 2004
Plasmacytoid dendritic cells(pDC)
Greenberg et al Ann Neurol, 57: 664, 2005
CD4+
T cells
B cells
MSAs in adult and juvenile disease
肌炎的临床诊断
临床分型
多发性肌炎
嗜酸性粒细胞肌炎
皮肌炎
肉芽肿性肌炎
免疫介导坏死性 局灶/结节性肌炎
肌炎
眶周肌炎
肿瘤相关性肌炎 包涵体肌炎
CTD相关性肌炎
多发性肌炎(PM)
皮肌炎(DM)
典型皮疹有诊断特异性 合并ILD常见且进展快 难治性皮疹考虑合并肿
瘤可能
无肌病性皮肌炎(ADM)
CD8+ T cells
CD8+
CD4+ T cells
B cells
Arahata & Engel Ann Neurol1984 Salajegheh M M&N 42:576, 2010
Plasma cells
Greenberg SA Neurol 65: 1782, 2005, Salajegheh M M&N 42:576, 2010
Hypothesis myositis and anti-
Jo-1
B
Trauma/Hypoxia
HMGB1
T
T
IFN-a,b T
B
T
T
IFN-a,b CD28null
IL-15
T
B
IL-1a, b
?
B
Ref: Casciola Rosen JEM 2005
DM (A&B): pDC producing Type I IFN (IFNα and β) dendritic cells (DC)
Eosinophilic myofasciitis
Granulomatous myopathy
DM: OVERLAP SYNDROMES SS and MCTD
Muscle biopsy
variable incidence of abnormal biopsy fiber atrophy: generalized or type II typical DM pathology unspecific inflammatory myopathy perimysial dense connective tissue vascular abnormalities vasculitis
2.皮下软组织炎性水肿（弥漫性）
T
T1W
STIR
PM/DM肌肉MRI表现
2.皮下软组织炎性水肿（弥漫性）
T1W
T2W
STIR
DM
STIR
PM/DM肌肉MRI表现
2.皮下软组织炎性水肿（局限性）
PM/DM肌肉MRI表现
3.肌筋膜炎
STI R
STIR
PM/DM肌肉MRI表现
4.脂肪沉积、肌肉萎缩
T1W
T2W
STIR
PM
STIR
PM/DM肌肉MRI表现
1.肌肉炎性水肿（局灶性分布）
T1W T2W
STIR DWI
1.肌P肉M炎/D性M水肌肿（肉散在性M分R布I）表现
STIR
T1W
STIR
PM/DM肌肉MRI表现
1.肌肉炎性水肿（弥漫性分布）
T1W
T2W STIR
STIR DM
PM/DM肌肉MRI表现
Observations from longitudinal studies –MHC class I in muscle fibers
Disease onset Muscle weakness
Diagnosis of PM/DM
Immunosuppressive treatment
Early phase
, Courtesy H. Gunawardena
Adaptive and innate immune system Uptake of autoantigen
Immune complex formation
B cell APC
autoantibody production
P C
Courtesy K. Amara
Severe necrotizing myopathy
Anti-
HMGCR Anti-SRP
Jo-1
Anti-SAE
Anti-Mi-
Ha
2
Zo
Myositis
Anti-synthetases
EJ
Severe DM (muscle, skin, soft tissue)
Hallmark DM
Anti-p140
B cell
HMGB1 pDC
B cell activation & differentiation
T cell activation & proliferation
IFNa
Th17
CD28null T cell
T reg
MHC II T Cell Receptor B Cell Receptor/ Fcγ Receptor B cell epitope T cell epitope
T1W
STIR
T2W
STIR
PM/DM肌ຫໍສະໝຸດ BaiduMRI表现
4.脂肪沉积、肌肉萎缩
正常肌肉T1W
病变肌肉T1W
PM/DM肌肉MRI表现
4.脂肪沉积、肌肉萎缩
T1W
FST1W
PM/DM肌肉MRI表现
脂 肪 浸 T1W 润 合 并 水 肿
STIR
PM/DM肌肉MRI表现
皮下及肌肉炎性水肿、肌肉萎缩脂肪浸润
MRI新技术在PM/DM应用
5.灌注加权像（PWI)
MRI新技术在PM/DM应用
6.肌肉纤维束示踪
肿瘤相关性肌病
肿瘤最常见于肌病发生的1-3年内出 现(60%) 肿瘤与肌病同时发生 肿瘤出现在肌病之前
伴发肿瘤的类 型
DM(白种人)：
MRI在PM/DM中的应用价值
确定诊断 累及范围及活动度评估 确定病变阶段 确定理想的活检部位
疗效评估 了解全身肌肉受累情况 肌肉外PM/DM相关疾病 鉴别诊断
MRI在PM/DM诊断中的应用
MRI检查序列
T1W
T2W
STIR
T2Wfs
DWI
T1Wfs+C
T1W 如何区分T1WI、T2WI、STIR
plasmacytoid DC (pDC) and myeloid DC (mDC)
PM / IBM (C&D): mDC producing Type II IFN, namely IFNγ C
A
B
Greenberg et al., 2005, Ann. Neurol.
D
Greenberg et al., 2007, Muscle Nerve.
Innate immune system Type I IFN, HMGB1 could interact with the adaptive immune system and may directly affect muscle fibres
Inflammatory cells in polymyositis and dermatomyositis
1.看TR、TE
T2WI：长TR（>2000毫秒）、
长TE（>50毫秒）
T1WI：短TR（﹤800毫秒）
短TE（﹤20毫秒）
T2W
STIR:长TR、长TE、有TI
2.看脂肪
T1W/T2W 高信号 STIR 低信号
STIR
3.看水
T1W
低信号
T2W 高信号；STIR 高信号
T1W
T2W
STIR
MRI在PM/DM诊断中的应用
T cells may be important in subsets of myositis and CD28null T cells may explain some of the treatment resistance. Specificity of T cells is not known
T1W
T2W
STIR
DM
STIR
MRI新技术在PM/DM应用
1.T2MAP
STIR
T2MAP
MRI新技术在PM/DM应用
2. DWI
STIR
DWI
MRI新技术在PM/DM应用
2.DWI
MRI新技术在PM/DM应用
4.MRS-1H
MRI新技术在PM/DM应用
4.MRS-1H
Subhawong TK, Wang X, Machado AJ, et al. 1H magnetic resonance spectroscopy findings in idiopathic inflammatory myopathies at 3T. Invest Radiol,2013;48(7):509-16.
T1W
T2W
STIR
T1Wfs+C
MRI在PM/DM诊断中的应用
T1W
脂肪
高
水
低
钙化
低
正常肌肉
低
肌肉水肿区
等或略低
肌肉脂肪浸润区
高
T2W 中、高
高 低 低 高 中、高
STIR 低 高 低 低 高 低
T1Wfs+C 低 低 低
均匀轻度强化 斑片状强化 低
PM/DM肌肉MRI表现
1.肌肉炎性水肿（局灶性分布）
PL-7 KS
Lung disease
OJ PL-12
Anti-MDA5
Anti-p155/140
TIF 1g
Cancer-DM
Myositis specific autoantibodies
CADM
Clinical phenotypes in adults and children
Gunawardena H. Rheumatology 2009;48:607-12. Review.
without inflammatory infiltrates
?
Classical time of diagnosis
Chronic phase
without inflammatory infiltrates
?
MHC class I in muscle fibers
MHC class I in muscle fibers Healthy individual
坏死性肌炎(NM)
是一组高度异质性疾病
Nearly all patients will present with subacute onset of proximal weakness that is very symmetrical and involves the pelvic as well as the shoulder girdle