Myositis Flashcards
Myositis classification
Adult onset DM: DM, Amyotrophic DM
Adult onset PM
Overlap myositis: ASA, Myositis assoc’d w/ CTD
Immune mediated necrotizing
IBM
Juvenile onset
Other: focal, giant cell, assoc’d w/ eosinophilia
**PM/DM diagnostic criteria **
Weakness
- Proximal painless weakness (no ocular/facial),
- Neck flexor weaker than extensor
- Pharyngeal (dysphonia),
- Upper esophageal (dysphagia)
- Characteristic rash (Heliotrope, Gotton’s)
- Elevated CK, aldolase, myoglobin, AST, ALT, LDH
- MSAs/MAAs: Jo1
- Abnormal EMG
- Muscle biopsy
DM rash biopsy*
Interface dermatitis with mucin (similar to SLE)
** IIM EMG**
- Increased insertional activity w/ SPONTANEOUS FIBRILLATION and complex repetitive discharge
- LOW AMPLITUDE and SHORT DURATION POLYPHASIC motor unit action potential. EARLY RECRUITMENT
- Positive SHARP waves (initial down spike then wide up wave)
** DM Derm Manifestations & where **
Heliotrope (eyelid, malar, forehead, nasolabial)
-V sign (chest/neck)
-Shawl sign (shoulders, prox arms)
-Holster sign (lat thigh)
-Gottrons (dorsal MCP/IP, extensor wrist elbow, knee)
- Mechanic’s hands - thickened crackened skin on dorsal/ventral surfaces of hands
-Nailfold: periungal erythema, cuticular overgrowth, dilated capillary loops
-Photosensitivity
-Subcutaneous calcification (JDM)
DM mimics
Trichinosis
-Allergic contact dermatitis
-Drug reactions (hydroxyurea, pencillamine, diclofenac, anti TNF)
Biopsy tips to max yield
MRI to direct
-Biopsy weak muscle opposite to that of EMG
-Do not biopsy muscle within 2-4weeks of EMG or within 3 mo of rhabdo
Adult onset DM clinical features
Rash (NO mechanic hands)
-Muscle disease (20% amyotrophic)
-MSA
** DM muscle biopsy pathology **
COMPLEMENT mediated (vs T cell mediated in PM): C5b-9 MAC found on cells
-Perimysial and/or PERIVASCULAR inflamm (VASCULATURE = primary target vs endomysial myocyte in PM)
-PERIFASCICULAR ATROPHY of muscle fibers
- Endomysial infiltration of mononuclear cells but NOT INVADING myofibers
- B cells, pDC, and CD4+ NOT CD8 like in PM
DM MSA’s and characteristics*
Mi-2 - rash, periungal/cuticle growth, weakness. NO CANCER OR ILD, good prognosis. ANA+
-SAE - rash, myositis, DYSPHAGIA, ILD; CANCER
-MDA5 - ULCERATION (nailfold, over joints, oral), palmar papules, arthritis, fever, RAPID ILD, often AMYOPATHIC, ANA negative, NO CANCER
-Tif1Gamma - rash, low titre ANA, CANCER
-NXP2 - rash, fingertip ulcers, JDM,subcutaneous calcification, CANCER
-*all can have CADM except MI-2
Antisynthetase (ASA) characteristics
- Proximal muscle weakness w/ elevated CK (5-10x ULN)
- Raynauds
- Mechanic’s hands (+/- Heliotrop/gottron)
- ILD
- Arthritis
- Fever
Antisynthetase (ASA) muscle pathology
Similarto DM but WITHOUT complement deposition
Perimysial pathology +/- perifasciular atrophy
Myositis assoc w/ CTD
-Which CTD and MAA
SSc: PM-SCl, RNP, Ku, U3RNP
-MCTD/SLE (RNP)
-Sjogrens (Ro)
ASA MSA’s and assoc’d manifestations
*all have myositis and ILD
Jo1: rash, seroneg arthritis, Raynaud, fever, negative cancer association
-PL7: ILD> myositis, mechanic hand, arthritis, Raynaud, esophageal
-PL12: ILD > myositis, Raynaud, pHTN
-EJ: rash,
-OJ: rash, arthritis, fever
Adult onset PM clinical features
Prox muscle weakness w/ elevated CK without other cause
-Cardiac (conduction, CHF)
-Increased cancer risk
** PM muscle histology **
- Endomysial > perimysial inflammation (CD8+ T cells)
- Endomysial infiltrates invade NON-NECROTIC fibers
- MHC class 1 on sarcolemma
- Vasculature SPARED
** Cancers assoc’d w/ DM/PM **
Adenocarcinoma:
- Breast, Ovary
- Lung
- GI: pancreas, stomach, colon,
- Taiwanese (nasopharyngeal and cervical)
-Hematologic: hematopoeitic cancer, and Hodgkin’s
** High risk for Cancer in IIM**
-Dermatomyositis
-TIF1γ
-NXP2
->40yo at IIM onset
-Persistent high dz activity despite tx (including relapse of previously controlled disease)
-Dysphagia (moderate to severe)
-Cutaneous necrosis or ulceration
Intermed Risk factors for Cancer in IIM
-Male sex
-IMNM: Anti-HMGCR
-PM: Anti-Mi2, SAE
-Anti-MDA5, CADM
Immune-mediated necrotizing myopathy (IMNM) clinical characteristics
-Myositis (prox weakness)
-MYALGIA
-HIGH CK 10-50xULN, rhabdo
-NO ILD/rash
-Rare assoc w cancer, HIV, ASA, another CTD
-Can be REFRACTORY to tx, bad prognosis
** Immune-mediated necrotizing myopathy (IMNM) muscle histology **
-Necrotic fibers
-Macrophage INVASION
-MINIMAL CD8+ T cells or lymphocyte infiltrate
Immune-mediated necrotizing myopathy (IMNM) MSA and manifestations*
BOTH have severe myositis
NEITHER have ILD, rash
-SRP - PAIN (necrosis), myocarditis, dysphagia. ANA neg
-HMGCR (aka 200/100) - Statin exposure (lovastatin, simvastatin) or cancer or red yeast rice or oyster/shitake mushroom.
DRB1*11:01 HLA
** IBM vs PM **
Demographic
Muscle involvement
Other organs
ANA
MSA
EMG
Response to therapy
- MC IIM >50
- SLOW onset
-Proximal AND DISTAL muscle (Knee/foot extensor, finger flexor); Asymmetric
-NO RASH, ILD, CANCER
-Other organs: neuropathy (vs ILD, arthritis, cardiac in PM)
-No MSA; sometimes ANA, C1NA
-EMG: myopathic and neuropathic
-POOR RESPONSE Tx
** IBM muscle biopsy histology pathology**
Similar to PM
-CD8+ T cell infiltrate
- No perifascicular atrophy
- MHC class 1 expressed
Unique:
-Rimmed vacuoles
-Ragged red fibers
-Amyloid deposits
-Eosinophilic cytoplasmic inclusion
IIM DDx
Drug/Toxin: statin, interferon alpha, colchicine, amiodarone, antimalarias, AZT, alcohol, GC, cocaine, antifungal, anti TNF
-Neuromuscular: muscular dystrophy, NMJ d/o (MG, ELS), Denervating (ALS)
-Endocrine: hypo/hyperTSH, acromegaly, cushing, addison
-Infectious: bacterial (staph, strep, borrelia), viral (HIV, adenovirus, influenza), parasitic (toxo, trichinella, taenia)
-Metabolic: Glycogen storage, abN lipid metabolism, mitochondrial myopathy, nutritional d/o (vit D/E), electrolyte d/o (hypoCa/Ca/K/PO4)
DM/PM Poor prognostic features
-Severe weakness
-Dysphagia
-Respiratory muscle involvement
-ILD
-Myocardial involvement
-Cancer
-MDA5
-Pathology: necrotizing myopathy
** Myositis Tx - nonpharm and pharm **
Pred 1-1.5mg/kg (up to 80mg/d) divided dose until remission (normal CK and strength ~4-6wk) - taper 20% monthly until 20mg, then 5mg monthly until 10mg x3-6mo before taper
-MTX 25mg/wk
-AZA 2-3mg/kg/d
-MMF 1-1.5g BID (ILD/rash)
-LFN
-CYC only if severe (eg MDA5 ILD) and JDM w/ vasculitis
-Tacrolimus 0.1mg/kg/kd; 2-5mg BID if resistant T cell mediated PM and lung dz
-Cyclosporine 3-5mg/kg/d
-IVIG 2g/kg x5d → monthly 2g/kg over 3d for severe refractory DM (esp dysphagia and HMGCR)
-RItux - 1g d1 and d15 → 1g q6mo
-Repository corticotropin injection - 80USP units SC twice a week x3 mo
-Nonpharm:
-rehab - passive/active assisted x4-6 weeks until strength and inflamm improves
-Vaccines
-OP
-PJP
** Steroid myopathy vs IIM exacerbation **
Steroid myopathy
- NO elevated CK/aldolase,
- NO MRI inflammation
- Acute (eg ICU) - prox + distal
- Chronic - proximal - pelvic > arms
- Biopsy - nonspecific atrophy of type 2b fibers WITHOUT inflamm infiltrate
** Risk factors for statin myopathy**
Statin characteristics: higher dose, lovastatin/simvastatin > others
-Other drugs inhibiting CYP3A4
-Other neuromuscular d/o: eg ALS
-Hypothyroidism
-Hypovitamin D
** 3 drugs which increase risk of statin myopathy**
CYP3A4 inhibitors: cyclosporin, macrolides, azole antifungals, HIV/HCV protease inhibitors
-Competitive CYP3A4 binders: colchicine with simvastatin.
-Drugs that also cause myopathy (gemfibrozil)
** Nonpharm contributor to statin myopathy **
Grapefruit consumption
-Strenuous exercises
-Hypothyroidism
-Vitamin D def (myalgia)
** FIVE elements that indicate a non-inflammatory cause in myopathies**
Muscle involvement: proximal AND distal, facial
-No inflammation: normal CK, ESR, CRP, no inflamm infiltate on bx
-Trigger: Exercise
-Not responding to steroids
-FamHx or early childhood
-EMG not showing myopathic
** Statin MSK manifestations**
Myalgia
-Asymptomatic hyperCK (neg MRI)
-Myositis
-Rhabdo (CK, myoglobinuria, AKI)
** 5 ways you can distinguish adult myotonic dystrophy from an inflammatory myositis**
Muscular dystrophy vs IIM
– Genetic vs Inflammatory
– Childhood (mostly) vs Adult (mostly)
– Proximal and distal vs Proximal
– Steroid response: none vs responsive
– Cardiomyopathy: Often vs not often
– AB: none vs myositis AB
– Biopsy: low/no dystrophin staining vs perimysial/perivascular inflamm
– Genetic testing for muscular dystrophy
Myositis antibody, name specific clinical finding: Jo1
MC AB for Antisynthetase
-PM/DM w/ ILD
Myositis antibody, name specific clinical finding: PL7
Antisynthetase
-PM/DM w/ ILD
ILD> myositis, mechanic hand, arthritis, Raynaud, esophageal
-OJ:
Myositis antibody, name specific clinical finding: PL12
Antisynthetase
-ILD more often than Myositis (clinically amyopathic)
-Raynaud
-pHTN
Myositis antibody, name specific clinical finding: EJ
Antisynthetase
-PM>DM w/ ILD
Myositis antibody, name specific clinical finding: OJ
Antisynthetase
-PM/DM w/ ILD
-Fever
Myositis antibody, name specific clinical finding: KS
Antisynthetase
-ILD more often than Myositis
Myositis antibody, name specific clinical finding: Zo
Antisynthetase
-ILD with Myositis
Myositis antibody, name specific clinical finding: Ha
Antisynthetase
-ILD with Myositis
Myositis antibody, name specific clinical finding: Mi2
DM w/ rash > muscle symptoms
-NO cancer or ILD
-Good prognosis (tx RESPONSIVE)
- ANA+
Myositis antibody, name specific clinical finding: MDA5
- DM (gottron, helitrope, shawl, V, holster)
- **Often AMYOPATHIC, CADM **
- Palmar papules
- Polyarthritis, fever,
- Alopecia
- ULCERATION (nailfold, over joints, oral),
- Less cancer but possible
-DM w/ rapidly progressive ILD
-Pneumomediastinum - ANA negative,
Myositis antibody, name specific clinical finding: Tif1G
-DM
-Classic DM Rash
-Low titre ANA
-MOST associated with cancer
Myositis antibody, name specific clinical finding: NXP2
DM - classic rash, finger tip ulcer,
-Subcutaneous calcification
-Juvenile DM
-Cancer associated
Myositis antibody, name specific clinical finding: SAE
- DM + mild ILD
-Cancer associated
-Dysphagia
Myositis antibody, name specific clinical finding: SRP
Severe, acute, resistant necrotizing myopathy
Myositis antibody, name specific clinical finding: HMG COA reductase
Necrotizing myopathy related to statin use in majority
DDX ILD with skin features, and NO muscles weakness
- SLE
- Sjogren’s
- ANCA vasculitis (especially MPO+)
- DM - MDA5/CADM
- DM - SAE (ILD is rare however)
- Antisynthetase syndrome (often have weakness)
- IPAF (interstitial PNA w/ autoimmune features)
** Causes of necrotizing myositis**
- Anti-SRP, HMGCR necrotizing myopathy (+/- statin exposure)
- Antisynthetase syndrome w/ necrotizing myopathy
- Cancer associated myositis
- Viral necrotizing myopathy: HIV, HCV
- Overlap syndrome necrotizing myopathy (SSc features/antibodies)
** Antisynthetase AB’s and their target**
Jo1
PL2/7
EJ/OJ
KS
Zo
Ha
**target against amino-acyl t-RNA synthetase
(eg Jo1 against cytoplasmic protein histidyl tRNA synthetase 1)
** Treatment for resistant skin dz in IIM**
Aggressive sun protection
Topical
Antipruritic
Antimalaria
Aza, MMF, MTX
Dapsone, IVIG, RTX, CNI
Tofa
** Causes of high CK **
Transient: exercise, trauma, seizure, psychosis
Cardiac: MI, arrhytmia, myocarditis
Neurogenic: radiculopathy, motor neuron disease (ALS), mononeuritis multiplex
Myopathic - acquired:
- Drugs (statin, EtOH, cocaine, chloroquine, colchicine, statins)
-Endocrine (hypo/hyperthyroid, hypoPTH, hypoK/PO4),
-IIM (PM, DM, IMNM)
- Infection: viral/fungal myositis
Myopathic - Inherited:
- Muscular / myotonic dystrophies,
- Metabolic myopathies
**Drugs causing muscle disease or elevated CK
- Antidepressants: TCA, venlafaxine, sertraline, escitalopram
- Antipsychotics: Seroquel, haldol, clozapine, olanzapine
- Antiretrovirals: tenofovir, abicavir, ralegravir
- Antimalarials
- Daptomycin
- Lithium
- Colchicine
- Statin
**Enzymes elevated in IIM
-Which is most sensitive vs specific **
-CK = most sensitive and specific
-Aldolase,
-Myoglobin,
- AST, ALT,
- LDH
** Extramuscular & extraderm Sx of DM/PM**
Constitutional symptoms
MSK
- Arthralgias,
- Arthritis (20-70%); associated with antisynthetase syndrome
Pulmonary:
- ILD (70% of patients with antisynthetase antibodies);
- Aspiration pneumonia;
- Respiratory muscle weakness,
- pHTN
GI:
- Esophageal dysmotility (10-30%);
- Reflux due to lower esophageal sphincter weakness (15-50%);
- Rectal incontinence due to sphincter ani weakness;
- Intestinal perforation due to vasculitis (more juvenile)
Cardiac:
- Arrhythmias,
- Conduction blocks,
- Myocarditis
Vascular:
- Raynaud’s (20-40%)
- Vasculitis (juvenile DM),
- Skin ulcerations (juvenile),
- Livedo reticularis,
Hyperthyroid vs Hypothyroid CK levels
Normal in Hyperthyroid
Elevated in Hypothyroid
** Components of NORMAL EMG (vs in myopathy) **
Insertional/spontaneous activity:
-should not have spontaneous activity (vs variable fibrillation and sharp waves in myopathy)
Motor unit analysis (amplitude, duration, # of phases, firing pattern)
- Morphology normal (vs small amplitude, short duration, increased polyphasia)
Recruitment - number of recruitable motor units
- Normal (vs early recruitment)
** Indications to order EMG **
Localize pathology of neuromuscular disorder: neurogenic vs myopathic, vs NMJ
Determine severity of suspected neuromuscular disorder
** How to tell neurogenic vs myopathic conditions apart on EMG **
Myopathic: EARLY recruitment = large number of motor units but SMALL amplitude, POLYphasic >4phases in a wave
Neurogenic: REDUCED recruitment bc axon/neuron loss but LARGE amplitudes
** How to differentiate demyelinating peripheral neuropathy and an axonal peripheral neuropathy by NCS and EMG **
NCS:
- Demyelinating: SLOWED conduction velocities with PRESERVED compound muscle action potential (CMAP)/sensory nerve action potential (SNAP) amplitudes
- Axonal neuropathies have REDUCED CMAP/SNAP amplitudes with PRESERVED conduction velocities.
EMG:
- Axonal neuropathies have EARLY denervation abnormalities
- Demyelinating neuropathies show denervation abnormalities LATER when axons are secondarily affected
3 similarities and 3 differences between the pathology for DM/PM
3 differences:
- Complement in DM (vs T-cell mediated in PM)
- Infiltrate CD4 predominant and other cells like B-cells, dendritic cells (DM) vs CD8 predominant (PM)
- Perivascular infiltrate (DM) vs endomysial infiltrate (PM)
- Perifascicular atrophy (DM) vs invasion of non-necrotic fibres (PM)
3 similarities:
- Upregulation of MHC1;
- Muscle fibre necrosis;
- Evidence of degeneration and regeneration
