General myositis
bilateral weakness in proximal muscles. You also note weakness of finger flexors and on hand grip strength assessment. What is it?
IBM, the most common IIM in patients aged over 50.
Bilateral, painless weakness develops insidiously and may be asymmetric. There is early involvement of distal muscles (foot extensor, finger flexors). Atrophy of forearms and quadriceps prominent which can lead to knee buckling with falls. Axial muscle weakness causes bent forward posture of spine. Dysphagia in 50%. No rash, ILD, or cancer association. May be associated with Sjögren’s syndrome.
MRI scan of the muscle can be helpful to direct muscle biopsy with a sensitivity of 96% to 100%. Areas of inflamed muscle demonstrate increased signal on T2-weighted images with fat suppression (short tau inversion recovery [STIR] images) but not on T1-weighted images, denoting areas of edema/inflammation.
what are gottron's papules
Gottron’s papules (60%–80% of DM patients): purple to erythematous flat or raised lesions over the dorsal sur- face of metacarpals and interphalangeal regions of the fingers (i.e., knuckles). Can also occur over extensor surfaces of the wrists, elbows, and knees.
Ulcerative skin lesions in an adult DM patient are highly associated with _______
Ulcerative skin lesions in an adult DM patient are highly associated with an underlying malignancy
Lower extremities are BOTH weak. You order MRI but forget to ask for T2 weighted images with fat suppression so it comes back normal. One week later you order EMG of the LEFT leg that shows spontaneous fibrillations, myopathic low-amplitude and short-duration polyphasic motor unit action potentials, and complex repetitive discharges. One week later the patient presents for the muscle biopsy you ordered... which leg should be biopsied?
the right leg
Describe mechanic's hand
Mechanic’s hand is common: characterized by cracking and fissuring of the skin of the finger pads, especially the radial side of the index finger
Which MSA of DM is most associated with malignacy?
Anti-TIF-1γ (p155/140): seen in 13% to 40% of DM patients who are typically aged over 60 years. It is highly associated with cancer. The sensitivity for diagnosing cancer-associated DM is up to 78% and specificity is 89%. The diagnostic odds ratio is 27, with a positive and negative predictive value of 58% and 95%, respectively. Patients usually present with classic DM rash that is frequently severe. Muscle disease may be low grade with normal CPK and elevated aldolase. The autoantibody targets TIF-1 family proteins, especially TIF-1γ. Notably TIF-1 proteins are interferon-responsive and have both positive and negative roles in carcino- genesis including p53 (tumor suppressor) regulation. Patients have a low-titer positive ANA with a speckled and homogenous pattern.
What is an MSA and MAA
MSAs and myositis-associated autoantibodies (MAA): Identify clinical subsets among the major categories of IIM. Patients with an IIM will only have one MSA since they are mutually exclusive. However, a patient with an MSA can also have a MAA particularly anti-Sjögren’s syndrome-related antigen A (SSA)/Ro (52kD).
Muscle disease predominates with acute or subacute onset of progressive proximal muscle weakness, myal- gias, very high CPK >10 to 50 times upper limit of normal. No ILD or rash. Rarely associated with cancer, HIV, ASA syndrome, or another connective tissue disease (e.g., systemic sclerosis). What is it?
Immune-mediated necrotizing myositis
Formerly lumped with PM. As its own separate category, it may account for 10% to 20% of all IIM. Also called necrotizing autoimmune myositis.
80% have an MSA:
- Anti-signal recognition particle (SRP)
- Anti-3-hydroxyl-3methylglutaryl-coenzyme reductase (HMGCR; 200/100 kDa)
Muscle histology: scattered necrotic fibers with macrophages. Minimal inflammatory infiltrate. No CD8+ T cells. MHC class I antigens and C5b-9 on sarcolemma of non-necrotic fibers.
What are the MSAs of ASA
anti Jo1 (histadyl tRNA synthetase)
Anti PL-7
anti PL12
anti EJ
Anti OJ
Which MSA of DM is not associated with ILD or malignancy?
Anti-Mi-2 (nucleosome remodeling-deacetylase [NuRD]): seen in 10%–15% of DM patients. Patients present with acute onset of classic skin (V- and shawl-sign), periungual/cuticle overgrowth, and muscle features of DM. Not associated with malignancy or ILD. Manifestations respond very well to corticosteroids (CS) with 5YS over 90%. The autoantibody targets the chromodomain helicase DNA-binding protein, which is a part of the NuRD complex that participates in the remodeling of chromatin by deacetylating histones. Patients have a positive antinuclear antibody (ANA) with speckled pattern.
Name the MSA associated with PM
No
Because there are no myositis-specific antibodies (MSAs) that are highly characteristic of polymyositis. While certain antibodies, such as anti-synthetase antibodies (e.g., anti-Jo-1), anti-SRP, and anti-Mi-2, can be found in some patients with polymyositis, they are not specific to this condition and are more commonly associated with other subtypes of idiopathic inflammatory myopathies. In fact, the presence of these antibodies often suggests a diagnosis other than pure polymyositis, such as antisynthetase syndrome, immune-mediated necrotizing myopathy, or dermatomyositis. Polymyositis is considered a diagnosis of exclusion, and it often lacks a specific serologic marker.
Previously ASA and IMNM were classified as subtypes of PM but this is no longer. We were trained in med school that anti-Jo1 is PM but this is no more. Its an ASA MSA.
Bilateral, painless weakness develops insidiously and may be asymmetric. Steroid trial does not help. Biopsy shows CD8 T cells invading healthy muscle fibers and ragged red fibers as well as amyloid deposits next to vacuoles. What is it?
IBM
Bilateral, painless weakness develops insidiously and may be asymmetric. There is early involvement of distal muscles (foot extensor, finger flexors). Atrophy of forearms and quadriceps prominent which can lead to knee buckling with falls. Axial muscle weakness causes bent forward posture of spine. Dysphagia in 50%. No rash, ILD, or cancer association. May be associated with Sjögren’s syndrome.
Muscle pathology: CD8+ T cells invading healthy muscle fibers. Increased MHC class I expression on muscle cells. Ragged-red fibers (abnormal mitochondria), red-rimmed autophagocytic vacuoles (Gomori–Trichrome stain), and amyloid deposits next to vacuoles are seen.
Slowly progressive and poorly responsive to immunosuppressive therapy. If you ever have PM patient not responding to prednisone, consider IBM.
Who's ready for biochem?
What are the antibodies of ASA syndrome directed against and what do these proteins do?
ASA MSAs are directed against amino-acyl t-RNA synthetases, which are in charge of facilitating amino acid binding to its cognate t-RNA
What do you call DM without muscle involvement and DM without skin involvement? Which is more common?
Amyopatic DM
- anti (SAE) small ubiquitin-like modifier-1 activating enzyme is the most common MSA of amyopathic DM. of those with rash only... half of them are always amyopathic and half end up getting myositis later.
DM sine dermatitis is super rare. Some people would call this PM, but if its perimysial inflammation with CD4 T cells and complement staining... and also has MSAs for DM... Its obvz DM sine dermatitis
Differentiate biopsy histologic findings of PM from DM from ASA
DM: perimysial/perivascular inflammation with (50%) or without (50%) perifasicular atrophy. Inflammatory infiltrate primarily B cells, CD4+ T cells, and plasmacytoid dendritic cells that produce interferon-α, which contributes to atrophy. Complement C5b-9 membranolytic attack complex found on endothelial cells associated with reduction of endomysial capillaries and microinfarcts.
PM: endomysial more than perimysial inflammation surrounding and invading non-necrotic muscle fibers expressing major histocompatibility complex (MHC) class I antigens. Inflammatory infiltrate comprises CD8+ T cells and macrophages. Vasculature is spared.
ASA: DM without complement
"defined as immune myopathy with perimysial pathology with or without perifasicular atrophy. Looks more like DM but no complement deposition. A few patients may have a biopsy that looks more like PM (endomysial inflammation) or IMNM"