Info
🌱 來自: Huppert’s Notes
Arthridities🚧 施工中
Arthridities
Osteoarthritis (OA)
• Pathogenesis: Progressive cartilage and meniscal degradation due to complex interplay of pathologic joint loading (due to obesity, joint malalignment, specific types of exercise or occupation, etc.) and dysregulated joint repair processes.
• Risk factors: Age >55 yr, female sex, obesity, acute or chronic joint injury
• Clinical features and diagnosis:
- OA is a clinical diagnosis made in a patient with compatible risk factors, joint pain that is worse with activity and relieved by rest, and absence of inflammatory features (e.g., absence of morning stiffness, absence of constitutional symptoms).
- Joint effusions may occur (particularly in the knees) but the WBC count will be <2K cells/μL.
- Radiographic hallmarks include:
• Joint space narrowing
• Subchondral sclerosis (i.e., increased bone density deep to cartilage)
• Subchondral cysts
• Osteophytes
• No erosions (with the exception of inflammatory (or “erosive”) OA of the hand)
• OA clinical phenotypes:
- Primary OA: Most common; no identifiable secondary cause. Typical joints = hands (especially 1st CMC, DIPs, PIPs), hips, knees, and cervical and lumbar spine. Involvement may be asymmetric.
- Secondary OA: Disease of the synovial joints resulting from a predisposing condition
• Local: Prior trauma (e.g., tibial plateau fracture), inflammatory/infectious arthritis or surgical intervention (e.g., ACL repair, meniscectomy) at the affected joint/joint space
• Systemic/metabolic: Hemochromatosis (2nd and 3rd MCPs and CMCs), hyperparathyroidism (wrists, MCPs), CPPD (MCPs, wrists, knees, hips), neuropathic arthropathy (such as in DM2), or OA-like pathologic changes accompanying inflammatory arthritis (such as psoriatic arthritis)
• Inflammatory hand OA:
- Associated with intermittent flares of swelling and redness of the affected joints (DIPs, PIPs) and erosions on hand X-ray
- The erosions are characteristically found in the central joint space, as opposed to the marginal (peripheral) erosions seen in RA
- Diffuse idiopathic skeletal hyperostosis (DISH): Characterized by calcification and ossification of the spinal ligaments and entheses, presenting with back pain and flowing osteophytes in the T spine on plain films (R side predominates in most cases)
• Treatments:
- Joint offloading: Work with occupational therapy/physical therapy to identify appropriate assistive devices (e.g., cane) or orthotics (e.g., thumb brace for 1st CMC OA)
- Exercise to strengthen periarticular muscles (potentially guided by physical therapy)
- Systemic and intra-articular pharmacotherapy (analgesic, not disease-modifying):
• NSAIDs
• Duloxetine
• Intraarticular glucocorticoids can be considered for knee and hip OA pain. Can be administered every 3 months (at which point pain relief effect tends to wane). No clear evidence of long-term harm with repeated injections, though one study showed an adverse effect on cartilage thickness (a finding that lacks any clear clinical correlate) (McAlindon et al. JAMA 2017).
- Surgical therapy: Knee or hip joint replacement provides pain relief and improves function for patients who have failed conservative therapy
Rheumatoid arthritis (RA)
• Pathogenesis: Mucosal inflammation triggers loss of tolerance to self-antigens in susceptible hosts, culminating in autoimmune destruction of synovial tissue.
• Epidemiology and risk factors: 0.5–1% prevalence in the general population, F:M = ~3:1. Increased risk in patients with periodontal disease and those who smoke cigarettes.
• Clinical features:
- Symptoms:
• Typically AM stiffness that lasts one hour, improves with activity, and is aggravated by rest
- Physical exam:
• Inflammatory polyarthritis with a predilection for the MCPs, PIPs, and MTPs with sparing of the DIPs of the upper and lower extremities. Variable involvement of the wrists, elbows, shoulders, hips, knees, ankles, and C-spine (characteristically involves the C1–C2 articulation; T- and L-spine are typically spared). Involvement is symmetric but severity may be asymmetric.
• Hand deformities: Ulnar deviation of MCP, Boutonniere deformities (contracture involving PIP flexion/DIP hyperextension), Swan-Neck deformity (contracture involving PIP hyperextension/DIP flexion)
- Radiographic hallmarks (plain film):
• Periarticular osteopenia (earliest finding), symmetric joint space narrowing, erosions (typically at the medial and lateral joint margins including the ulnar styloid), and alignment deformities including subluxation and ulnar deviation of the MCPs
- Lab findings:
• Rheumatoid factor (Rf; 50% patients have positive Rf in first 6 months; 75–85% by 2 yr)
• Anti-cyclic citrullinated peptide (CCP) antibodies: More specific than Rf (sensitivity 70%, specificity 95%)
• 10–20% of cases are seronegative (e.g., Rf-negative, anti-CCP-negative)
• ESR and/or CRP is elevated in 75% of patients
- Extra-articular manifestations:
• Derm: Rheumatoid nodules (30% of patients) occurring at pressure points including the olecranon; neutrophilic dermatoses including pyoderma gangrenosum and Sweet syndrome; small vessel cutaneous vasculitis may occur in patients with a history of smoking and/or longstanding RA
• Cardiac: Independent risk factor for CAD and CHF; pericarditis
• Pulm: Air trapping reflecting small airway inflammation in 50%, clinically apparent ILD in 10%; bronchiolitis; bronchiectasis; pleuritis (typically complicated exudative effusion with low pH/low glucose); cricoarytenoid arthritis (rare complication, presents with hoarseness, dysphagia, and stridor)
• Eyes: Sicca symptoms/secondary Sjögren’s; episcleritis; scleritis; keratitis
• CNS: Mononeuritis multiplex due to peripheral nerve entrapment; c-spine subluxation can lead to cervical myelopathy (rare)
• Heme: Anemia of inflammation; Felty syndrome (rare autoimmune condition characterized by the triad of neutropenia, splenomegaly, and longstanding seropositive RA); increased risk of large B cell lymphomas
• Diagnosis: ACR/EULAR criteria: See Table 9.10.
TABLE 9.10 • Rheumatoid Arthritis Classification Criteria (2010 ACR/EULAR)
• Symptom monitoring:
- The Simplified Disease Activity Index (SDAI) incorporates tender and swollen joint counts, CRP level, and a clinician and patient-derived global assessment.
- SDAI <3.3 defines remission according to the ACR/EULAR guidelines.
• Treatment:
- Methotrexate is the first-line disease-modifying antirheumatic drug (DMARD)
• Titrate to the maximum tolerated dose (up to 25 mg weekly) at 12-week intervals
• At doses >15 mg weekly, consider subcutaneous dosing to improve bioavailability
• Contraindications to methotrexate include liver disease, advanced CKD, and heavy alcohol use
• Leflunomide can be used as first-line DMARD if there are contraindications to methotrexate use
• 30–50% of paitents respond to methotrexate monotherapy
- For patients who do not respond to methotrexate, consider adding:
• Sulfasalazine and hydroxychloroquine
• A TNF-α inhibitor
• Rituximab
• Tocilizumab
• Tofacitinib
- Additional considerations:
• Prednisone 5–10 mg daily may be used to rapidly improve symptoms while awaiting therapeutic effect of disease modifying anti-rheumatic drugs (DMARDs)
• Methotrexate/hydroxychloroquine/sulfasalazine combination therapy may have similar efficacy to methotrexate and TNF-α inhibitor
• Patients with a very low SDAI score at diagnosis may be candidates for sulfasalazine or hydroxychloroquine monotherapy
- Pregnancy:
• Pre-existing RA improves during pregnancy in 2/3 of cases and has a stable or worsening course in the other 1/3.
• Methotrexate and leflunomide are contraindicated in pregnancy
• Hydroxychloroquine and sulfasalazine are safe in pregnancy