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.
