✅ Inflammatory myopathies / Flashcards
Ddx: Idiopathic Inflammatory myopathies (Polymyositis/Dermatomyositis/IBM)
Idiopathic Inflammatory myopathies (Polymyositis/Dermatomyositis/IBM)
Inclusion body myositis
Hypothyroidism
Diabetes mellitus
Drug- and alcohol-induced muscle disease
Infections
SLE, systemic sclerosis, Sjögren syndrome, amyloidosis, vasculitis, rheumatoid arthritis
Critical illness neuromyopathy
Rhabdomyolysis
Still Disease
Idiopathic Inflamatory myopathies (Polymyositis/Dermatomyositis/IBM)
Hx: Proximal muscle weakness
Physical exam: Heliotrope rash, shawl sign, grotons papules (hyperkeratotic red papules and plaques over bony prominences), rash (heliotrope rash on the upper eyelids and periorbital area, photosensitive rashes involving the shoulders, neck, and anterior chest)
Labs: elevated CK, EMG,Biopsy, Anti Mi/Jo
Dermatomyositis: CD4-positive T cells around the muscle fascicles and in the perimysial areas.
Tx: Steroids
Dermatomyositis (DM)
is a systemic autoimmune disease characterized by Myopathy: proximal muscle weakness (eg, difficulty climbing stairs, combing hair), elevated muscle enzymes (eg. Creatinine kinase, aldolase) resembling polymyositis, but with additional inflammatory skin findings: heliotrope rash (erythematous or violaceous edematous eruption on the upper eyelids and periorbital skin) Gottron’s papules (raised erythematous plaques over the joints and bony prominences of the hands). Muscle biopsy is diagnostic and shows mononuclear perimysial infiltrates, perifascicular atrophy, and patchy necrosis.
Dermatomyositis may occur alone or as a paraneoplastic syndrome of an underlying malignancy. The most commonly associated cancers include ovarian, lung, colorectal, and non-Hodgkin lymphoma. Symptoms may precede the diagnosis of malignancy but often parallel the course of the cancer.
Dermatomyositis: Causal mechanism is immunologic, with autoantibody production of anti-Mi2, anti-Jo1, or anti-SRP. The condition is often due to underlying bronchogenic, gastric, or colorectal carcinoma.
Antinuclear antibody titers are frequently elevated in dermatomyositis, although anti-Jo-1 is more specific. Muscle biopsy confirms the diagnosis and shows a perimysial inflammatory infiltrate, patchy ischemia and necrosis, and perifascicular atrophy and fibrosis.
Dermatomyositis: CD4-positive T cells around the muscle fascicles and in the perimysial areas.
Inclusion body myositis
Also an inflammatory muscle disease that causes asymmetric proximal and distal weakness; more common than polymyositis in older people; does not respond well to glucocorticoids and immunosuppressants. Biopsy showing evidence of filamentous inclusions is diagnostic.
Still Disease
Hx: Systemic inflammatory disorder characterized by quotidian (daily) fever, evanescent rash, arthritis, and multisystem involvement.
Dx: Based on the typical clinical presentation and exclusion of infection and malignancy, particularly leukemia and lymphoma.
Leukocytosis, anemia, thrombocytosis, elevated erythrocyte sedimentation rate, elevated serum ferritin level (≥1000 ng/mL [1000 µg/L]), and abnormal liver chemistry tests; antinuclear antibody titer and rheumatoid factor typically are negative.
Fibromyalgia
Fibromyalgia is characterized by widespread pain and tenderness of at least 3 months’ duration.
Hx: Youg to middle-aged woman.
Chronic widespread pain
Fatigue, Impaired concentration
Px: Tenderness at trigger points
Dx: > 3 months of symptoms with widespread pain index or symptom severity score
Normal labs
Tx: serotonin-norepinephrine reuptake inhibitor (SNRI)
Limited Cutaneous Systemic Sclerosis = CREST
Calcinosis (High BP vessel disease)
Raynaud’s
Esophageal
Sclerodactyly
Telangectaias (GI bleeds, Iron deficiency anemia)
Dx: Anti-centromere antibodies
Pulmonary arterial hypertension (PAH) is also common in the limited cutaneous subtype of SS. PAH results from intimal (smooth muscle layer) hyperplasia of the pulmonary arteries and typically presents with progressive dyspnea. Patients may also experience exertional syncope or presyncope (eg, lightheadedness) due to right ventricular (RV) failure and inadequate venous return to the left atrium.
Px: Demonstrates RV heave (or parasternal heave), which is an impulse palpated immediately to the left of the sternum that suggests RV enlargement. A loud pulmonary component of the second heart sound and signs of right heart failure (eg, peripheral edema, hepatomegaly) may also be present.
Diffuse Cutaneous Systemic Sclerosis = Scleroderma
CREST + Visceral Involvement
Lung (ILD, DPLD)
Heart (Constrictive pericarditis)
Kidney (renal crisis) - ACE inhibitor
Dx: Anti-topoisomerase/Scl70
Systemic lupus erythematosus (SLE)
Autoantibodies can take the form of immune complexes that deposit in tissues or bond to target cells.
Can cause damage by fixing complement on the surface of a cell (causing cell lysis), by binding to Fc receptors on circulating cells (leading to cell clearance in the liver or spleen), or by binding to Fc receptors on macrophages (initiating cell-mediated inflammation).
Hx: Most common in women of childbearing age; women are 9 times more likely than men to be affected by SLE. Environmental influences (eg, ultraviolet [UV] light), infection by the Epstein-Barr virus, smoking, stress, and hormonal factors likely contribute to SLE development or disease flares. The most common agents associated with drug-induced lupus are procainamide, hydralazine, isoniazid, and quinidine.
Nonspecific constitutional symptoms are common in SLE and include fatigue, fever, and weight loss. Mucocutaneous findings, such as nasal and oral ulcers, alopecia, or rash (malar or discoid) are found in up to 90% of patients with lupus. Additionally, greater than 90% of patients with SLE have polyarthralgias or polyarthritis. Symmetric wrist or hand (metacarpophalangeal [MCP], proximal interphalangeal [PIP] joints) involvement is most common.
SLE is associated with Raynaud phenomenon, which is characterized by the fingers or toes becoming white or blue when cold and then red when warmed. SLE is also associated with Sjögren syndrome, as evidenced by dry eyes and dry mouth.
ANA is found in 95% to 99% of patients with SLE but lacks specificity. ANA also is found in patients with viral and bacterial infections, other autoimmune diseases, malignancies, and cirrhosis and in up to 10% of the normal population
Dx: A patient is classified as having SLE if 4 of the 11 American College of Rheumatology criteria for SLE diagnosis are confirmed by a physician: To establish the diagnosis of SLE, patients need not manifest all the diagnostic criteria simultaneously; the criteria can be fulfilled over time.
<strong>Malar rash</strong>
Fixed erythema, flat or raised, over the malar eminences (spare the nasolabial folds and under the lower lip)
<strong>Discoid rash</strong>
Erythematous, circular, raised patches with keratotic scaling and follicular plugging; atrophic scarring may occur (commonly occur on the external ear, forearm, and scalp; scalp lesions may cause alopecia).
<strong>Photosensitivity</strong>
Rash after exposure to ultraviolet light
<strong>Oral ulcers</strong>
Oral and nasopharyngeal ulcers (observed by physician)
<strong>Arthritis</strong>
Nonerosive arthritis of ≥2 peripheral joints, with tenderness, swelling, or effusion (Tendon inflammation may lead to joint rupture or Jaccoud arthropathy).
<strong>Serositis</strong>
Pleuritis or pericarditis (documented by electrocardiogram, rub, or evidence of effusion)
<strong>Kidney disorder</strong>
A patient satisfies this criterion by having a 24-hour urine protein excretion >500 mg/d, (or 3+ protein) by urinalysis showing >10 erythrocytes per high-power field or erythrocyte or leukocyte casts in a sterile urine sample (proven by culture), or by kidney biopsy. Urinalysis: or >0.5 g/d; cellular casts;
<strong>Neurologic</strong>
Neurologic deficits, seizures, or confusion may indicate central nervous system infection, ischemia, brain or spinal cord inflammation (cerebritis or transverse myelitis), or the more subtle neuropsychiatric manifestations. Sensory or motor symptoms may be due to peripheral neuropathy, muscle inflammation, or ischemia caused by <strong>vasculitis</strong>.
<strong>Hematologic</strong>
Anemia is most often due to chronic disease, but can also occur as a result of autoimmune hemolytic anemia (AIHA). Cytopenias: leukopenia (<4000/µL [4.0 × 109/L]) or lymphopenia (<1500/µL [1.5 × 109/L]) or thrombocytopenia (<100,000/µL [100 × 109/L]) in the absence of offending drugs. Idiopathic thrombocytopenic purpura (ITP) may be the first presenting symptom of SLE. Evans syndrome, which is the occurrence of two or more immune-mediated cytopenias (usually AIHA and ITP), may also be a manifestation of SLE.
<strong>Immunologic</strong>
Anti–double-stranded DNA, anti-Smith, and/or antiphospholipid antibodies
Antinuclear antibodies (ANA)
An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in the absence of drugs known to induce ANA
Patients with a high pretest probability of SLE and positive ANA assay (usually a titer ≥1:160) should undergo confirmatory testing using a more specific autoantibody study with either an anti-dsDNA antibody assay or an anti-Smith antibody assay. Anti-dsDNA antibodies are present in approximately 50% to 70% of patients with SLE and generally are not found in those with other autoimmune diseases. Patients with a new diagnosis of SLE should also undergo screening for anticardiolipin antibodies and the lupus anticoagulant.
In active SLE, the circulating immune complexes activate complement, causing their consumption and resulting in a decrease of C3, C4, and total hemolytic complement (CH50).
Antiphospholipid syndrome can be associated with SLE or can occur in isolation. Diagnosis includes both clinical and laboratory criteria.
Hx: Antiphospholipid syndrome is associated with venous thromboembolism (59%), arterial thromboembolism (28%), pregnancy loss, vasculitis, and cardiac valvular abnormalities.
Dx: May be initially considered when a patient has unexplained thrombocytopenia or the activated partial thromboplastin time (aPTT) is prolonged and does not improve with a mixing study. Positive anticardiolipin antibodies (IgG or IgM) or lupus anticoagulant in the setting of previous arterial or venous thromboembolism or pregnancy morbidity make the diagnosis of antiphospholipid syndrome.
Lupus nephritis: hypertension, ankle edema, hematuria, proteinuria, and erythrocyte casts on urinalysis
To prevent irreversible kidney damage, early treatment with a high-dose glucocorticoid is indicated for patients whose condition raises strong suspicion for lupus nephritis.
Tx: Musculoskeletal complaints: Methotrexate or, occasionally, low-dose glucocorticoids may be necessary if a patient fails to respond to initial therapies or the initial manifestations are more severe. should be treated with NSAIDs or hydroxychloroquine.
Photosensitive rashes can be treated conservatively with a sunscreen that blocks UVA and UVB radiation, hydroxychloroquine, and topical glucocorticoids.
High-dose or pulse-dose (high doses over a short period of time) glucocorticoids (such as methylprednisolone) and other immunosuppressive agents (eg, cyclophosphamide, mycophenolate mofetil, azathioprine) are used for the more severe manifestations of SLE, including nephritis, cerebritis, vasculitis, and life-threatening hematologic abnormalities.
Cyclophosphamide is generally reserved for lupus nephritis, given its serious side effect profile. Recent studies suggest that mycophenolate mofetil is effective for lupus nephritis with a more favorable side effect profile.
Because patients with SLE may have functional asplenia, vaccination against pneumococcal illness, Haemophilus influenzae infection, influenza, and, possibly, meningococcal infection is indicated.
Patients with SLE and positive antiphospholipid antibodies should be treated with low-dose aspirin (81 mg daily).
Sjogrens syndrome
Sjögren syndrome is characterized by sicca syndrome, which causes xerophthalmia (dry eyes), and xerostomia (dry mouth). The absence of oral mucosal moisture often causes difficulty with mastication and swallowing and increases the risk for dental caries and periodontal disease. Vaginal dryness and parotid gland enlargement are frequently present, and mild fatigue and arthralgia are common.
Dx: Abnormal findings on the Schirmer test, which measures moisture under the lower eyelids, are consistent with Sjögren syndrome.
Approximately 50% of patients with this syndrome are antinuclear antibody positive and 60% to 75% of patients with primary Sjögren syndrome are anti-Ro/SSA antibody positive, and approximately 40% of these patients are anti-La/SSB antibody positive.
Mixed connective tissue disease (MCTD)
A systemic autoimmune condition with clinical features of SLE, systemic sclerosis, and polymyositis. Patients may present with joint pain (arthralgia), myalgias, pleurisy, esophageal dysmotility, and Raynaud’s phenomenon (vasospasm of distal extremities in response to cold temperatures). Because there is overlap of clinical features, it is suggested that the disease is not a distinct entity, but rather a subset of SLE, systemic sclerosis, and polymyositis. Over time, patients with MCTD may progress to the SLE or systemic sclerosis.
One distinguishing feature of this disease is high antibody titers to U1-ribonucleoprotein (RNP), which is involved in splicing machinery. Elevated titers of RF and ANA are also common in MCTD, but non-specific. MCTD is readily treatable with corticosteroid therapy.
Pulmonary hypertension is a common cause of death in MCTD. Unlike in systemic sclerosis, pulmonary hypertension in MCTD is not due to fibrosis of the lungs, but by intimal proliferation and medial hypertrophy of pulmonary arterioles.
In MCTD, renal involvement is uncommon – unlike in SLE, systemic sclerosis, and polymyositis.
Antineutrophil cytoplasmic antibodies (ANCAs)
are circulating antibodies that react with cytoplasmic antigens, and were previously classified according to their intracellular distribution: cytoplasmic (c-ANCA) or perinuclear (p-ANCA). They are now named according to their target antigen:
Anti-myeloperoxidase (MPO-ANCA, formerly p-ANCA) targets the lysosomal granule involved in oxygen free radical generation
Anti-proteinase-3 (PR3-ANCA, formerly c-ANCA) PR3 is a neutrophil granule constituent.
