Arthritis Associated with Systemic Disease, and Other Arthritides¶
Chapter 386 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders · Part 11 – Rheumatology & Immunology · Chapter 386
Key Clinical Points¶
- Acromegaly arthropathy involves joint space widening (initially) due to cartilage hypertrophy; hallmark is involvement of 2nd/3rd MCP joints in hemochromatosis.
- Hemochromatosis: Arthropathy affects 20–40% of patients, often starting after age 50; hooklike osteophytes seen in up to 20%.
- Hemophilia: Hemarthrosis is common in both types (A and B); fever >38.3^circ ext{C} (101^circ ext{F}) indicates potential infection.
- Sickle Cell Disease: Dactylitis occurs in children <5 years; 40% of patients are hyperuricemic, leading to possible gouty arthritis.
- Neuropathic Joint (Charcot): Progresses due to loss of pain/proprioception; common in DM (sim 0.5%) at age ge 50.
- Hypertrophic Osteoarthropathy (HOA): Characterized by periostitis and new bone formation; associated with pulmonary, GI, cardiovascular, or thyroid conditions.
- Tietze Syndrome: Defined by painful swelling of costochondral articulations (usually 2nd/3rd), unlike costochondritis (pain without swelling).
- Fibromyalgia treatment includes muscle relaxants, antidepressants (e.g., Duloxetine), and anticonvulsants (e.g., Pregabalin).
- MRI is more sensitive than bone scan for early detection of avascular necrosis in sickle cell disease.
- Hemochromatosis arthropathy may present as the first clinical feature of the disease.
DEFINITION & CLASSIFICATION¶
• Definition (Harrison's 22e): Arthritis associated with systemic disease refers to joint manifestations that occur as a result of underlying systemic conditions rather than primary rheumatologic disorders. • Classification: Can be either inflammatory or non-inflammatory.
EPIDEMIOLOGY¶
• Acromegaly: Diagnosis typically between 40 and 50 years (5% are <20 years). • Hemochromatosis: Arthropathy begins after age 50; may be the first clinical feature. • Hemophilia: Hemarthrosis occurs after 1 year of age (when child begins to walk/run). • Neuropathic Joint Disease: Incidence in DM is \sim 0.5%, usually at ≥ 50 years.
ETIOLOGY & PATHOPHYISIOLOGY¶
• Acromegaly: Excess growth hormone (GH) and insulin-like growth factor I → stimulates cartilage, periarticular connective tissue, and bone. • Hemochromatosis: Iron storage disorder; excess intestinal absorption → iron deposition in parenchymal cells. ◦ Mechanisms of joint damage: → Catalyzes superoxide-dependent lipid peroxidation → Interferes with collagen formation → Increases release of lysosomal enzymes → Inhibits synovial tissue pyrophosphatase (in vitro) → potential chondrocalcinosis. • Hemophilia: Sex-linked recessive; deficiency of factor VIII (Type A, 85% of cases) or factor IX (Type B). • Hemoglobinopathies: → Sickle Cell: Musculoskeletal abnormalities due to sickling and infarction. → β-Thalassemia: Bone/joint issues due to marrow expansion; iron staining in bone trabeculae, osteoid, cement line, and synovium. • Neuropathic Joint Disease: Loss of pain sensation/proprioception → loss of protective mechanisms → repeated trauma → progressive cartilage/bone damage. • Hypertrophic Osteoarthropathy (HOA): Periostitis followed by new bone formation; triggered by circulating cells or growth factors bypassing lung clearance.
CLINICAL FEATURES¶
Acromegaly Arthropathy¶
• Presentation: Enlarged hands/feet, spadelike distal tufts, barrel chest. • Joint Involvement: Osteoarthritis of knees, shoulders, hips, wrists, and fingers. • Radiographic Findings: → Initial: Joint space widening (cartilage hypertrophy). → Later: Joint space narrowing as cartilage degrades. • Synovial Fluid: Usually noninflammatory; may contain calcium pyrophosphate crystals → acute calcium pyrophosphate arthritis.
Hemochromatosis Arthropathy¶
• Presentation: 20–40% of patients; often first clinical feature after age 50. → Affects small joints (hands) then larger joints (knees, ankles, shoulders, hips). • Key Diagnostic Clue: Involvement of 2nd and 3rd MCP joints (not typical for routine OA). • Radiographic Findings: → Subchondral sclerosis, cysts, and juxtaarticular proliferation. → Hooklike osteophytes in 20% of patients. • Synovial Fluid: Noninflammatory; \sim 50% have calcium pyrophosphate deposition.
Hemophilic Arthropathy¶
• Presentation: Spontaneous hemarthrosis (common in both Type A and B). → Severity related to degree of clotting factor deficiency. • Acute Hemarthrosis: Warm, tensely swollen, painful joint; blood remains liquid for ≥ 1 week. • Complications: → Chronic noninflammatory, fibrotic arthropathy (swollen joints, flexion deformities). → Muscle bleeding (e.g., iliopsoas) → hip flexion contracture. → Compartment syndrome (calf/forearm) → muscle necrosis and neuropathy. → Pseudotumors (distal to elbows/knees in children; femur/pelvis in adults).
Hemoglobinopathies¶
• Sickle Cell Disease: → Dactylitis: Hand-foot syndrome, common in kids <5 years (1–3 weeks duration). → Osteomyelitis: Common in long tubular bones; often caused by Salmonella. → Avascular Necrosis (AVN): Affects femoral head (\sim 5%), humeral head, etc. → Gouty Arthritis: Up to 40% of patients are hyperuricemic → polyarticular attacks. • Thalassemia: → β-Thalassemia Major/Intermedia: Symmetric ankle arthropathy (2nd-3rd decade) due to marrow expansion. → β-Thalassemia Minor: Seronegative oligoarthritis or acute asymmetric arthritis.
Hyperlipidemia¶
• Familial Hypercholesterolemia: → Migratory polyarthritis (knees, large joints) → sudden onset, 2 days to 2 weeks. → Tendinitis (Achilles, patellar) often precedes xanthomas. • VLDL/Triglyceride Elevation: Mild inflammatory arthritis in middle age; radiographic juxtaarticular osteopenia and cysts. • Xanthomas: Tuberous (subcutaneous) or tendinous (within fibers).
Neuropathic Joint Disease¶
• Pathology: Progressively enlarged joints due to bony overgrowth and synovial effusion. • Clinical Presentation: Less pain than expected from damage; 'rocker foot' in DM (convexity of sole). • Distribution by Condition: → Tabes dorsalis: Hips, ankles. → Syringomyelia: Glenohumeral joint, elbow, wrist. → Diabetes: Tarsal and tarsometatarsal joints.
Hypertrophic Osteoarthropathy (HOA)¶
• Clinical Features: Clubbing and periostitis of distal extremities.
Tietze Syndrome & Myofascial Pain¶
• Tietze Syndrome: Painful swelling of costochondral articulations (usually 2nd/3rd). • Myofascial Pain: Localized pain with tender points; deep aching pain.
DIFFERENTIAL DIAGNOSIS¶
• Hemochromatosis vs. OA: Hemochromatosis specifically involves 2nd/3rd MCP joints and may present earlier than typical OA. • Tietze Syndrome vs. Costochondritis: Tietze includes swelling; costochondritis is pain without swelling. • Septic Arthritis vs. Hemarthrosis: Hemarthrosis may have low-grade fever, but fever >38.3^circ ext{C} (101^circ ext{F}) suggests infection.
DIAGNOSTIC APPROACH¶
- Initial Clinical Assessment: Identify systemic triggers (e.g., hyperglycemia for Charcot, iron overload for Hemochromatosis, growth hormone excess for Acromegaly).
- Synovial Fluid Analysis: → Noninflammatory: Suggests hemarthrosis, hemochromatosis, or hyperlipidemia. → High neutrophil count (sterile): Suggests synovial infarction in sickle cell.
- Radiographic Imaging: → Hemochromatosis: Look for hooklike osteophytes and 2nd/3rd MCP involvement. → Sickle Cell: Use MRI to detect early avascular necrosis (more sensitive than bone scan).
- Laboratory Testing: → Hemochromatosis: Ferritin and iron/total iron-binding capacity. → Sickle Cell: Check uric acid levels for gouty arthritis.
MANAGEMENT & TREATMENT¶
Hemophilia¶
- Initial Management: Avoid nonselective NSAIDs.
- Alternative Analgesia: Use COX-2 inhibitors or factor replacement.
- Infection Protocol (if fever >38.3^circ ext{C}): → Aspirate joint → culture fluid → start broad-spectrum antibiotics (including Staphylococcus coverage).
Sickle Cell Disease¶
- Infection: Treat with appropriate antibiotics for osteomyelitis.
- Avascular Necrosis: Joint replacement may be required to reduce pain and improve function.
Fibromyalgia (Table 385-3)¶
- Muscle Relaxant: Cyclobenzaprine (10–40 mg daily, at bedtime or in divided doses up to 4x/d).
- Antidepressants: → Amitryptiline (10–50 mg/d; start at bedtime). → Duloxetine (60 mg/d; start at 30 mg/d for 1 week). → Milnacipran (50 mg bid; titrate over 7 days).
- Anticonvulsants: Pregabalin (50 mg bid; titrate over 7 days).
- Analgesic: Tramadol (37.5 mg tramadol + 325 mg acetaminophen up to 4x/d).
Other Conditions¶
- Hemochromatosis: Treat underlying iron overload.
- Hyperlipidemia: Use lipid-lowering agents (monitor for myopathy/myositis if on HMG-CoA reductase inhibitors).
- Neuropathic Joint: Weight-bearing restriction.
PROGNOSIS & COMPLICATIONS¶
• Hemophilia: Chronic noninflammatory, fibrotic arthropathy and joint contractures. • Sickle Cell: Avascular necrosis can lead to joint destruction; osteomyelitis may cause bone loss. • Neuropathic Joint: Progressive destruction of cartilage and bone leading to 'rocker foot' and potential ulceration.
KEY PEARLS & HIGH-YIELD POINTS¶
• Hemochromatosis: 2nd/3rd MCP joint involvement is a key clinical clue. • Sickle Cell: Dactylitis is rare after age 5; avascular necrosis occurs in \sim 5%. • Neuropathic Joint: Diagnosis of Charcot is based on the loss of pain sensation leading to mechanical destruction. • HOA: Associated with a wide range of conditions (Table 386-3) including pulmonary, GI, and cardiovascular diseases.
Reference Tables¶
TABLE 385-3 Pharmacologic Agents Effective for Treatment of Fibromyalgia DRUG Muscle relaxant Antidepressants: balanced…¶
Harrison's 22e, p.2966
| DRUG | DOSE |
|---|---|
| Muscle relaxant Cyclobenzaprine Antidepressants: balanced serotonin-norepinephrine reuptake inhibitors Amitryptilinea Duloxetineb,c Milnacipranb,c Anticonvulsants: ligand of the alpha-2-delta subunit of voltage- gated calcium channels Pregabalinb Analgesic Tramadol |
10–40 mg daily, at bedtime or in divided doses up to 4×/d 10–50 mg/d; recommended to take at bedtime 60 mg/d; begin at 30 mg/d for 1 week 50 mg bid; titrate over 7 daysd 150–450 mg/d; begin at 75 mg bid for at least 1 week 37.5 mg tramadol + 325 mg acetaminophen up to 4×/d |
| 386 | Arthritis Associated with Systemic Disease, and Other Arthritides Carol A. Langford, Brian F. Mandell |
TABLE 386-1 Musculoskeletal Abnormalities in Sickle Cell Disease Sickle cell dactylitis Joint effusions in sickle cell…¶
Harrison's 22e, p.2967
| Sickle cell dactylitis | Avascular necrosis |
|---|---|
| Osteomyelitis | Septic arthritis |
| Infarction of bone marrow | Synovial infarction |
TABLE 386-2 Disorders Associated with Neuropathic Joint Disease Diabetes mellitus Tabes dorsalis Meningomyelocele…¶
Harrison's 22e, p.2969
| Diabetes mellitus | Amyloidosis |
|---|---|
| Meningomyelocele | Congenital indifference to pain |
TABLE 386-3 Disorders Associated with Hypertrophic Osteoarthropathy Pulmonary¶
Harrison's 22e, p.2971
- Pulmonary
Bronchogenic carcinoma and other neoplasms
Lung abscesses, empyema, bronchiectasis
Chronic interstitial pneumonitis
Cystic fibrosis
Sarcoidosis
Gastrointestinal
Inflammatory bowel disease
Sprue
Neoplasms: esophagus, liver, bowel
Cardiovascular
Cyanotic congenital heart disease
Subacute bacterial endocarditis
Infected arterial graftsa
Aortic aneurysmb
Aneurysm of major extremity arterya
Patent ductus arteriosusb
Arteriovenous fistula of major extremity vessela
Thyroid (thyroid acropachy)
Hyperthyroidism (Graves’ disease)