17. Connective Tissue Disorders Flashcards
Systemic Lupus Erythematosus (SLE)
A multisystem chronic inflammatory disorder characterized by autoantibody production responsible for immune-mediated tissue damage.
- Women child-bearing age. AA, Asian, Hispanics. Wide clinical variance.
- Constitutional symptoms (fever, fatigue, weight gain), arthralgias, pancytopenia, photosensitive rash, serositis.
- Procainamide is known to cause drug-induced SLE that will resolve after discontinuation.
Multisystem manifestations of SLE
RENAL: majority of SLE. Immune complex-mediated glomerulonephritis which may result in hypoalbuminemia. Oliguric renal failure may result as GFR is reduced.
PULMONARY: Pleuritis in up to 30% of patients sometime in course of disease. Pleural effusions, pulmonary arterial hypertension, chronic interstitial lung disease. PFTs show restrictive lung pattern.
CARDIAC: Pericarditis in 50% of patients with SLE (usually small and asymptomatic). Libman-Sacks endocarditis. Advanced atherosclerosis. More prone to cardiac arrhythmias. Hydroxychloroquine is known to cause prolonged QT.
MAXILLOFACIAL: cutaneous and mucous membranes. Lichenoid lesions, non-descript erythematous patches, granulomatous lesions buccal mucosa, hard palate. Butterfly facial rash.
HEMATOLOGY: all three blood cell lines. Anemia of chronic disease (normochromic, normocytic). Low serum iron and lower transferrin. Hemolytic and aplastic anemia. Leukopenia and thrombocytopenia in 50%. HIgher risk of thromboembolism due to presence of antiphospholipid antibodies.
NEUROPSYCHIATRIC: acute confusional state, seizures, mood disorders, psychosis, aseptic meningitis, optic neuritis, and central and peripheral neuropathies.
Diagnosis of SLE
Based on constellation of symptoms and not serological testing alone.
- 50% will not have met four criteria at one time, but will have during the course of their disease.
- ANA most common specific antibody found in SLE
- Anti-DSDNA and anti-Sm are more specific.
Mnemonic for SLE
DOPAMINE RASH
- Discoid rash
- Oral ulcers
- Photosensitivity
- Arthritis >2 joints
- Malar rash
- Immunologic criteria: anti-Sm Ab, anti-DSDNA
- Neurologic symptoms: seizures, psychosis
- ESR elevated
- Renal disease
- ANA positive
- Serositis: pleurisy, pericarditis
- Hematologic disorders: hemoytic anemia, leukopenia, thrombocytopenia
Treatment of SLE
- NSAIDs to control arthritis and serositis
- Avoid sun exposure (photosensitivity)
- Corticosteroids limited to acute/subacute symptomatology, effective at managing thrombocytopenia and hemolytic anemia as well as suppressing glomerulonephritis and cardiovascular abnormalities.
- Topical steroids for cutaneous and mucosal lesions.
- Antimalarial drugs such as hydroxychloroquine (Plaquenil) long term to control disease flare-ups. Long term use can lead to eye toxicity.
- Severe disease symptoms require immunosuppressant agents such as alkylating agents (cyclophosphamide), purine synthesis inhibitors (azathioprine) and disease modifying agents such as methotrexate (folate agonist). Consider biologic agents (rituximab, belimumab) for refractory cases.
Perioperative management SLE
- Consult rheumatologist
- Delay elective surgery until flare-ups have resolved
- Preop labs CBC, aPTT, BMP (r/o anemia, thrombocytopenia, coagulopathies, renal compromise, and electrolyte disturbances).
- EKG
- Auscultation
- Supplemental antibiotics in setting of immunosuppression
- Steroid supplementation for adrenal suppression
- Avoid nephrotoxic drugs, maintain urine output
- Airway considerations: laryngeal inflammation, vocal cord paralysis, subglottic stenosis,
Rheumatoid Arthritis
Chronic systemic inflammatory disease of unknown etiology characterized by inflammatory polyarthritis (synovitis) with progressive destruction of joint, bone, and articular cartilage.
- Females:Males 3:1
- 5th to 6th decade
- Symmetrical polyarthropathy (joints involved warm to touch). Morning stiffness and swelling are hallmark signs.
- Ulnar deviation and subluxation of MCP joints, swan-neck deformity, and Boutonniere deformities
- Differs from osteoarthritis which involves weight-bearing joints.
Multi-system manifestation of RA
CARDIO: pericarditis, myocarditis, CAD, aortitis (aortic dilatation, aortic regurg, advanced atherosclerosis).
OCULAR: keratitis, scleritis, episcleritis leading to eye pain and redness.
NEURO: neuropathy secondary to deposition of complexes
PULMONARY: pleural effusions and rheumatoid nodules. Restrictive lung disease due to costochondral joint involvement.
HEMATOLOGICAL: anemia of chronic disease. Felty’s syndrome (RA with splenomegaly and leukopenia). Small vessel vasculitis.
Diagnosis of RA
Not based solely on lab results
- Rheumatoid factor titers increased
- Elevated erythrocyte sedimentation rate
- Elevated C-reactive protein
Diagnostic criteria (symptoms >6 weeks and 4/7 criteria)
- morning stiffness
- swelling of 3+ joints
- swelling of hand joints
- symmetrical swelling
- subcutaneous nodules
- serum rheumatoid factor
- radiographic evidence of erosive arthritis
Treatment of RA
- Anti-inflammatory drugs like corticosteroids (prednisone)
- Disease-modifying antirheumatic drugs (DMARDs) to slow progression (methotrexate, hydroxychloroquine, antimalarials, minocycline, tofacitinib/Xeljanz)
- Monoclonal antibody biologics: entanercept (Enbrel), infliximab (Remicade), adalimumab (Humira) work by inhibiting TNF-alpha
How does methotrexate work?
Methotrexate acts by inhibiting metabolism of folic acid via dihydrofolate reductase. Close monitoring is required to monitor for liver dysfunction and bone marrow suppression.
How do monoclonal antibody biologics such as entanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) work?
Inhibit TNF-alpha
What is osteoarthritis
OA is a painful degenerative process involving progressive deterioration of articular cartilage and remodeling of subchondral bone that is not primarily inflammatory.
Risk factors osteoarthritis
Age, female gender (post-menopausal), obesity, smoking, trauma from physical activity, occupation of physical nature, and muscle weakness
Pathophysiology osteoarthritis
Changes in the cartilage progresses through roughness, fibrillation, fissuring, and eventual erosion of the cartilage. This activates chondrocytes to release proteolytic enzymes causing further degeneration. Unprotected bone results in thinnning leading to subchondral cysts early on and later to subchondral sclerosis as bone formation is outpaced by bone resorption.
What is obesity
Abnormally high amount of adipose tissue compared with lean muscle mass with an excess body weight >20% over predicted ideal body weight.
How is BMI calculated
body weight (kg) / height (m^2)
Obesity hypoventilation syndrome
“Pickwickian syndrome” - episodic central apnea events due to desensitization of hypercarbia.
What is muscular dystrophy?
Group of inheritable myopathies causing progressive death of muscle fibers.
- Commonly due to breakdown of dystrophin-glycoprotein complex
- Symmetric wasting of muscles without skeletal muscle denervation
Types of muscular dystrophy (3)
Duchenne Muscular Dystrophy (Pseudohypertrophic Muscular DystrophY)
Becker Muscular Dystrophy
Myotonic Muscular Dystrophy
Anesthetic considerations muscular dystrophy
Patients may be on high dose steroids (reduce muscle necrosis, prolong ambulation), ACE inhibitors (reduce myocardial fibrosis), beta blockers (reduce oxygen demands on heart), Digoxin (cardiac failure)
Cardiomyopathy is expected. Desfluorane is agent of choice, otherwise consider TIVA to reduce risk.
Succinylcholine is contraindicated due to risk of rhabdomyolysis and hyperkalemia. Use rocuronium (non-depolarizing agent).
High risk of MH (halothane inhalation or succinylcholine).
Delayed gastric emptying.
Pulmonary aspiration due to pharyngeal muscle weakness.
Decreased pulmonary reserve and respiratory muscle weakness (prolonged mechanical ventilation). Limit narcotics.
What is myasthenia gravis?
Autoimmune disorder affecting postsynaptic neuromuscular transmission of the nicotinic ACH receptor due to production of autoantibodies.
- Characterized by weakness and fatigue of the skeletal muscles with improvement at rest.
How is myasthenia gravis diagnosed?
Anti-acetylcholine receptor antibody test is the confirmatory diagnostic test of choice.
Edrophonium chloride (tensilon) test. Patient injected with anticholinesterase with improved strength (often diagnostic in patients with ptosis or ophthalmoparesis.
Treatment of Myasthenia Gravis
Pyridostigmine (anticholinesterase) is first line of treatment
Immunosuppresants (prednisone, cyclosporine, fujimycin (Tacrolimus), and IV immunoglobulin) to attenuate immune destruction of acetylcholine receptors
Anesthesia considerations myasthenia gravis
Consider reduced or avoidance of sedatives or opioids in those with reduced respiratory reserve.
Possible need for prolonged ventilatory support.
Avoid neuromuscular blocking drugs if possible (especially long-acting) due to variable response and treament with anticholinesterases. Usually RESISTANT to succinylcholine and SENSITIVE to non-depolarizing muscle relaxants.
RSI. Succinylcholine adjusted to 1.5-2mg/kg.
What is Ehlers-Danlos Syndrome?
EDS is a group of inheritable diseases that result from a defect in synthesis or structure of fibrillar collagen leading to changes in skin, tendons, blood vessels, and viscera
Autosomal dominant
Types of EDS
80% of cases fall under classical and hypermobile types.
There are six major subtypes.
Vascular EDS subtype is life-threatening due to spontaneous rupture of small and large arteries.
Classical features of EDS (classical and hypermobile subtypes)
Joint hypermobility with common subluxation, double jointed fingers.
Skin hyperelasticity/hyperextensibility
Gorlin sign (can touch tongue to tip of nose)
Abnormal scarring, soft skin, easily bruised, hernias common.
Patient management EDS
Minimize skin tape
Can be resistant to local anesthetic
TMJ subluxation during intubation
Higher risk of occipitoantlantoacial instability
Pneumothorax risk (reduce airway pressures)
POTS in hypermobile varient, ensure adequate hydration
Avoid NSAIDs due to bruising risk
Cardiac eval due to risk of aortic root dilatation and mitral valve prolapse propensity, usually non-significant
May have poor periodontal health
Subtypes with vascular fragility should have type and crossmatch
26% of patients have platelet aggregation defects (consider prophylactic TXA)
___% of patients with EDS have a platelet aggregation defect
26%
What is Marfan’s Syndrome?
AD connective tissue disorder affecting cardiac, skeletal, and ocular tissue.
- Mutation in extracellular matrix protein fibrillin-1 leading to structural deformities in connective tissue.
Diagnosis of Marfan’s syndrome
PCP, cardiology, ophthalmology, geneticist, orthopedist
Ghent criteria
Skeletal characteristics Marfan’s disease
- Dolichostenomelia (overgrowth of long bones, tall and thin).
- Pectus carinatum or pectus excavatum
- Thoracolumbar scoliosis
- Protusio acetabuli (inward bulge of acetabulum of the hip)
- Long fingers compared to palm
- Joint hypermobility (Steinberg “thumb” sign) - thumbnail extends beyond ulnar side of hand when fingers are folded over thumb
(Walker-Murdoch “wrist” sign) - thumb and fifth finger nail beds overlap when encircling the wrist
Cardiac features of Marfan’s disease
AV valve thickening leading to prolapse
Aortic dissection/aneurysm due to weakened arterial media
Mitral valve prolapse
Ocular features of Marfan’s disease
Ectopia lentis
Severe myopia
Hypoplastic iris
Predisposed to retinal detachment, early onset glaucoma
Antimongoloid slants
Facial features of Marfan’s disease
Dolichocephaly
Enophthalmos
Retrognathia
Micrognathia
Malar hypoplasia
High arched palate
Therapies for Marfan’s disease
Beta blockers (reduced HR is protective for aortic root growth, reduce hemodynamic stress)
Angiotensin II receptor blockers for protection against aortic root dilatation
ACE inhibitors to reduce volume overload 2/2 valvular dysfunction
Lifestyle changes including avoidance of stimulants, breathing against resistance, and contact sports
