Differential Diagnosis of Polyarthralgia
Critical First Step: Distinguish Arthralgia from Arthritis
The most important initial determination is whether objective joint swelling (synovitis) is present on physical examination—this distinguishes true arthritis from arthralgia and fundamentally changes the differential diagnosis. 1, 2
Key Distinguishing Features
- Arthralgia: Joint pain WITHOUT visible or palpable swelling 2
- Arthritis: Joint pain PLUS objective synovitis (swelling visible or palpable on exam) 1, 2
- Morning stiffness >30-60 minutes strongly suggests inflammatory arthritis rather than simple arthralgia 1, 2
- Dramatic response to NSAIDs/corticosteroids within 24-48 hours (but not opioids) indicates inflammatory process 1, 2
- Metacarpophalangeal squeeze test positive (difficulty making fist or pain with compression) suggests underlying inflammation 1
Differential Diagnosis Categories
Inflammatory Causes (Most Urgent to Exclude)
Infectious Etiologies
- Septic arthritis: Requires urgent arthrocentesis if suspected; presents with fever, chills, systemic symptoms, significantly elevated CRP/ESR, bacteremia 3, 4
- Viral infections: Arboviral infections (chikungunya, dengue) cause severe polyarthralgia with travel history to tropical/endemic regions and systemic febrile illness 1, 4
- Lyme disease: Migratory joint pain/swelling, erythema migrans in 60-80% of cases, tick exposure in endemic areas 1
- Acute rheumatic fever: Migratory polyarthritis after group A streptococcal infection in moderate-to-high risk populations; dramatic response to salicylates/NSAIDs within 24-48 hours 3, 1, 4
- Reactive arthropathies: Consider after autoimmune, viral causes excluded 3
Autoimmune/Inflammatory Arthritides
- Rheumatoid arthritis: Symmetrical polyarthritis of small joints (MCPJs, PIPJs), characteristic erosions, anti-CCP or RF positivity, elevated CRP/ESR 3, 5
- Psoriatic arthritis: Psoriasis (current, history, or family history), inflammatory articular disease, nail dystrophy, dactylitis, juxta-articular new bone formation on hand/foot radiography, DIP joint involvement 3
- Axial spondyloarthritis: Inflammatory back pain, sacroiliitis, asymmetrical inflammatory arthritis, enthesitis, dactylitis, uveitis, HLA-B27 positivity, pain responsive to NSAIDs 3, 4
- Systemic lupus erythematosus: Consider with systemic symptoms 3, 6
- Gout: May superimpose on pre-existing osteoarthritis 3
Non-Inflammatory Causes
Degenerative
- Osteoarthritis: Older age, history of strain or dominant side involvement, bony swelling, subchondral sclerosis/cysts, osteophytes, joint space narrowing on imaging 3, 7, 5
- Hand osteoarthritis (HOA): Pain on usage, mild morning stiffness (<30 minutes), targets DIP, PIP, thumb base joints; confident diagnosis in adults >40 years with typical features (Heberden/Bouchard nodes, bony enlargement) 3
Metabolic/Systemic
- Paget's disease: Family history, pelvic/skull localization, raised alkaline phosphatase, age >50 years, mixed osteolytic/osteosclerotic imaging 3
- Osteomalacia: Generalized bone pain, muscle weakness, low serum phosphate, elevated alkaline phosphatase, low vitamin D 3
- Hypophosphatasia: Generalized bone pain, muscle weakness, dental abnormalities, low alkaline phosphatase 3
- Hemochromatosis: Mainly targets MCPJs and wrists 3
Other Conditions
- Chronic non-bacterial osteitis (CNO): Consider with bone marrow edema on MRI, typical skeletal sites (anterior chest wall, spine, mandible) 3
- Tietze's syndrome: Pain in costosternal transitions, unilateral, self-limiting after weeks-months 3
- Fibrous dysplasia: Bone deformities, expansive lytic ground-glass lesions 3
- Malignant bone tumor: Unexplained weight loss, solitary lesion with rapid growth, cortical destruction 3
Diagnostic Evaluation Algorithm
History Documentation
- Onset, duration, pattern: Migratory vs. persistent, symmetric vs. asymmetric, acute vs. chronic (≥6 weeks increases likelihood of persistent inflammatory arthritis) 1, 4, 7
- Morning stiffness duration: >30-60 minutes suggests inflammatory process 1, 2
- Response to medications: NSAIDs/corticosteroids vs. opioids 1, 2
- Systemic symptoms: Fever, weight loss, rash, recent infections 4, 7
- Travel history: Endemic areas for arboviral infections 1, 4
- Prior streptococcal infection: Consider acute rheumatic fever 1, 4
Physical Examination
- Complete rheumatologic examination of ALL peripheral joints for tenderness, swelling, erythema, warmth, range of motion 1, 4, 7
- Spine examination including range of motion and tenderness 4
- Metacarpophalangeal squeeze test 1
- Pattern assessment: Symmetric vs. asymmetric, small vs. large joints 4, 7
- Extra-articular manifestations: Skin findings, nodules, eye involvement 7
Laboratory Workup
- Inflammatory markers: ESR and CRP (caveat: normal values do NOT exclude inflammatory disease) 1, 4
- Autoimmune panel: ANA, RF, anti-CCP antibodies if symptoms persist >4 weeks 1, 4
- Additional tests based on presentation: HLA-B27 (spondyloarthritis), creatine kinase (myositis), troponin (if muscle weakness present) 4
- Complete blood count, urinalysis, metabolic panel may provide useful diagnostic clues 7
Imaging Studies
- Plain radiography of affected joints initially to evaluate for erosions, joint damage, or metastatic lesions 4, 5
- MRI: Preferred for detecting bone marrow edema, soft tissue involvement, early disease features; particularly useful in CNO diagnosis 3, 4
- Ultrasound: Point-of-care musculoskeletal ultrasound can detect synovitis and predict RA development 4, 5
Indications for Rheumatology Referral
Refer immediately if:
- Clinical joint swelling (synovitis) is present 1, 4, 2
- Symptoms persist >4 weeks without clear alternative diagnosis 1, 2
- Severe pain with signs of inflammation despite initial management 1, 4
- Persistent monoarthritis (to exclude septic arthritis, malignancy, chronic infection) 2
Common Clinical Pitfalls
- Do NOT wait for chronic symptoms to develop before referring—early referral is indicated if clinical synovitis is present 1, 2
- Normal inflammatory markers do NOT exclude inflammatory disease 1, 4
- Prior NSAID use may mask migratory nature of acute rheumatic fever polyarthritis—obtain careful medication history 3
- Polyarthralgia is highly nonspecific—in low-risk populations, it is almost always a symptom of illness other than acute rheumatic fever 3