Differentials of RA
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Differential Diagnoses of Rheumatoid Arthritis
RA is a clinical diagnosis with no single pathognomonic finding. Its early manifestations overlap considerably with many other conditions. The differentials are best organized by category:
1. Other Connective Tissue / Idiopathic Arthritides
| Condition | Distinguishing Features |
|---|---|
| Adult-onset Still's disease | Fever >39°C for >1 week; leukocytosis >10,000/mm³ with >80% PMNs; evanescent salmon-colored rash; sore throat; lymphadenopathy; splenomegaly; markedly elevated serum ferritin |
| Systemic Lupus Erythematosus (SLE) | Non-erosive arthritis with reducible deformities (Jaccoud's arthropathy); positive ANA, anti-dsDNA; ACPA negative; internal organ involvement especially renal; malar rash, oral ulcers |
| Spondyloarthropathy (PsA, ReA, AS, IBD-associated) | Male predominance; often oligoarticular with large joint/lower extremity distribution; low back involvement; HLA-B27+; RF/ACPA negative; uveitis; psoriasis, dactylitis, IBD associations |
| Sjögren's syndrome | Keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth); salivary gland enlargement; ANA+ (SS-A/SS-B); often RF+ but ACPA negative |
| Vasculitis | Seronegative polyarthritis with systemic fever; end-organ involvement; markedly elevated ESR/CRP; ANCA positive |
| Polymyalgia Rheumatica (PMR) | Shoulder and hip girdle involvement; markedly elevated ESR/CRP; RF/ACPA negative; associated with giant cell arteritis; >50 years old |
| RS3PE syndrome (Remitting seronegative symmetric synovitis with pitting edema) | Synovial thickening + pitting edema of hands; elderly men; very steroid-responsive; RF/ACPA negative; malignancy association |
| Sarcoidosis | Acute form (Löfgren's syndrome): erythema nodosum + bilateral hilar adenopathy; predilection for ankles; often RF+ but ACPA negative; non-caseating granulomas on biopsy |
| Fibromyalgia | Widespread myalgia without true inflammatory arthritis; RF/ACPA negative; normal ESR and CRP |
| Palindromic rheumatism | Episodic, self-resolving joint inflammation with pain-free intervals; can evolve into RA |
| Multicentric reticulohistiocytosis | Destructive arthritis + characteristic skin nodules; negative serology |
2. Infection-Related
| Condition | Distinguishing Features |
|---|---|
| Parvovirus B19 | Non-erosive arthritis; typically seronegative; self-limited; parvovirus IgM+; viral prodrome (slapped cheek, aplastic crisis) |
| Hepatitis B and C | Non-erosive arthritis similar to RA; RF+; ACPA negative; hypocomplementemia; positive HBV/HCV serology; cryoglobulins |
| Bacterial endocarditis | High fever; predominantly large joints; audible murmur; positive blood cultures; peripheral emboli; can be RF+ but ACPA negative |
| HIV | Brief acute joint pain with initial viremia, then oligoarticular process; fever |
| Chikungunya | Insect-borne virus; acute febrile illness with rash followed by polyarthritis |
| Rheumatic fever | Migratory polyarthritis following streptococcal pharyngitis; ASLO positive; RF negative; carditis, chorea, erythema marginatum |
| Post-streptococcal arthritis | Non-erosive; antecedent group A strep infection; ASO positive; RF negative |
| Septic arthritis | Monoarticular (usually); acute, hot, red joint; fever; elevated WBC; positive joint fluid cultures |
| Lyme arthritis | Large joint (knee) involvement; positive Lyme serology; tick exposure history |
3. Crystal Arthropathies
| Condition | Distinguishing Features |
|---|---|
| Gout (chronic tophaceous) | Tophi can mimic rheumatoid nodules; RF negative; elevated uric acid; monosodium urate crystals (negatively birefringent) on joint aspiration; asymmetric |
| Calcium pyrophosphate disease (CPPD/pseudogout) | Chondrocalcinosis on X-ray; calcium pyrophosphate crystals (weakly positively birefringent); RF negative; predilects knees, wrists |
4. Degenerative / Mechanical
| Condition | Distinguishing Features |
|---|---|
| Osteoarthritis (erosive) | DIP and PIP joints (Heberden's and Bouchard's nodes); no systemic inflammation; RF/ACPA negative; normal ESR/CRP; X-ray: joint space narrowing + osteophytes (not erosions) |
| Psoriatic arthritis | Can be symmetric and polyarticular (like RA); look for nail changes (pitting, onycholysis), psoriatic plaques, dactylitis ("sausage digit"); RF/ACPA typically negative |
5. Miscellaneous / Special Contexts
| Condition | Distinguishing Features |
|---|---|
| Hypothyroidism | Rheumatic manifestations (arthralgias, myopathy); TSH elevated; also co-exists with RA so must be checked regardless |
| Paraneoplastic arthritis | Especially in elderly with fulminant-onset seronegative symmetric synovitis; RS3PE pattern; investigate for underlying malignancy |
| Reactive arthritis | Post-infectious (GI or GU); classic triad: arthritis, urethritis, conjunctivitis ("can't see, can't pee, can't climb a tree"); RF/ACPA negative; HLA-B27+ |
Key Serological Discriminators (Goldman-Cecil)
| Condition | Subcutaneous Nodules | RF |
|---|---|---|
| Viral arthritis (Hep B/C, Parvo, Rubella) | - | ± |
| Bacterial endocarditis | ± | + |
| Rheumatic fever | + | - |
| Sarcoidosis | + | + |
| Reactive arthritis | - | - |
| Psoriatic arthritis | - | - |
| SLE | ± | + |
| Primary Sjögren's | - | + |
| Chronic tophaceous gout | + | - |
| CPPD | - | - |
| Polymyalgia rheumatica | - | - |
| Erosive OA | - | - |
Practical Approach
A patient >18 years with symmetric small-joint arthritis (hands/feet), morning stiffness >30 minutes, positive RF or ACPA is likely RA. However, early RA mimics several conditions. Key steps:
- Serology: RF, ACPA, ANA, anti-dsDNA, ANCA, complement, Hep B/C, parvovirus IgM, ASO
- Imaging: X-rays for erosions vs. osteophytes; chondrocalcinosis
- Joint aspiration: Crystals, culture, WBC count
- History & exam: Rashes, nail changes, oral ulcers, dactylitis, uveitis, murmur, prior infections
- Labs: CBC, CRP, ESR, uric acid, TSH, LFTs
Sources: Rheumatology 2-Volume Set (Elsevier, 2022); Firestein & Kelley's Textbook of Rheumatology; Goldman-Cecil Medicine
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