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)