What is the differential diagnosis for a 65-year-old patient with anemia, slightly elevated C-Reactive Protein (CRP), foot pain, and metatarsal erosion?

Differential Diagnosis for 65-Year-Old with Anemia, Elevated CRP, Foot Pain, and Metatarsal Erosion

The most likely diagnosis is erosive inflammatory arthritis, with rheumatoid arthritis and gout being the primary considerations, followed by psoriatic arthritis and septic arthritis as critical rule-outs. 1, 2

Primary Differential Diagnoses

Erosive Inflammatory Arthritis (Most Likely)

Rheumatoid Arthritis (RA)

• Advanced age, female gender if applicable, and involvement of small joints of hands and feet are highly predictive of RA 1
• Metatarsal erosions with elevated CRP strongly suggest inflammatory arthritis, particularly RA 1
• Anemia of chronic disease commonly accompanies RA and correlates with disease activity 1
• The combination of normocytic anemia with elevated acute phase reactants (CRP) is characteristic of chronic inflammatory conditions 1, 3
• Obtain rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) immediately, as these are highly predictive of RA diagnosis and prognosis 1

Erosive Osteoarthritis

• Targets interphalangeal joints primarily but can affect metatarsophalangeal joints 1
• Characterized by abrupt onset, marked pain, inflammatory symptoms (stiffness, soft tissue swelling), and mildly elevated CRP 1
• Shows radiographic subchondral erosion with potential progression to marked bone attrition 1
• CRP levels correlate with radiographic severity and number of joints involved in erosive OA 1

Gout (Crystal Arthropathy)

• Monoarthritis of the first MTP joint has 99% sensitivity for gout when presenting acutely 2
• Bony erosion on X-ray supports chronic tophaceous gout with acute flare 2
• Elevated CRP with normal ESR is characteristic of acute crystal inflammation 2
• Normal white blood cell count does not exclude gout 2
• Joint aspiration for monosodium urate crystal analysis remains the gold standard and must be performed 2

Critical Rule-Outs

Septic Arthritis

• Must be excluded urgently in any warm, painful joint with erosive changes 2
• Elevated CRP supports infection, though absence of fever and normal WBC make it less likely 2
• Arthrocentesis with cell count, differential, and culture is mandatory before initiating treatment 2

Psoriatic Arthritis

• Can target distal interphalangeal joints or affect just one ray 1
• Elevated CRP with normal ESR can occur in seronegative spondyloarthropathies 2
• Look for psoriatic skin lesions, nail changes, and dactylitis 1

Hemochromatosis

• Mainly targets metacarpophalangeal joints and wrists but can involve feet 1
• Consider in patients with elevated liver enzymes (note the patient's clinical context) 1
• Check serum ferritin, transferrin saturation, and iron studies 4, 5

Diagnostic Algorithm

Immediate Laboratory Evaluation

Essential First-Line Tests:

• Complete blood count with differential to characterize anemia (microcytic, normocytic, or macrocytic) and assess for leukocytosis 1, 5
• Serum ferritin to distinguish iron deficiency from anemia of chronic disease 4, 5
• ESR measurement alongside CRP, as both should be performed at baseline for diagnosis and prognosis 1, 3
• RF and ACPA testing, as these are predictive of RA diagnosis even when negative tests don't exclude progression 1

Additional Autoantibody Testing (if indicated):

• Antinuclear antibodies (ANA) if connective tissue disease suspected 1
• HLA-B27 if spondyloarthropathy features present 1

Metabolic and Renal Assessment:

• Comprehensive metabolic panel including creatinine (chronic kidney disease causes anemia) 5, 6
• Serum uric acid level for gout evaluation 2
• Liver function tests and glucose 3

Critical Procedural Intervention

Arthrocentesis of Affected Metatarsal Joint:

• Perform immediately if infection suspected or to confirm crystal arthropathy 2
• Send synovial fluid for cell count with differential, Gram stain, culture, and polarized microscopy for crystals 2
• This is the gold standard for differentiating septic arthritis, gout, and inflammatory arthritis 2

Imaging Studies

Radiographic Evaluation:

• X-rays of hands, wrists, and feet should be performed at baseline, as presence of erosions is predictive for RA and disease persistence 1
• Metatarsal erosions help distinguish inflammatory arthritis from degenerative disease 1
• Repeat radiographs within 1 year to assess progression 1

Advanced Imaging (Selected Cases):

• MRI of hands and feet may be considered if RA suspected and diagnosis unclear 1
• Ultrasound can differentiate erosive from non-erosive arthritis but has limited ability to distinguish between subtypes 1

Anemia Evaluation Specific to This Case

Pattern Recognition:

• Anemia with elevated CRP suggests anemia of chronic disease from inflammatory arthritis 1, 6
• Serum ferritin level is the preferred initial diagnostic test to distinguish iron deficiency from chronic disease 4, 5
• If ferritin is low (<46 ng/mL), iron deficiency anemia is confirmed and requires gastrointestinal evaluation in a 65-year-old 4, 5
• If ferritin is elevated or normal-high with anemia, this supports anemia of chronic disease 5, 6

Age-Specific Considerations:

• In patients older than 65 years with iron deficiency anemia, 9% have gastrointestinal cancer when evaluated 4
• Endoscopy beginning with colonoscopy is recommended for patients older than 50 with iron deficiency 4, 5

Common Pitfalls and Caveats

Laboratory Interpretation Errors:

• Anemia and azotemia can artificially elevate ESR independent of inflammatory activity 3
• Normal ESR does not exclude inflammatory arthritis; CRP may be more sensitive in acute crystal arthropathy 2
• Serum uric acid may be normal during acute gout flare 2

Diagnostic Delays:

• Failing to perform arthrocentesis when infection is possible can lead to joint destruction 2
• Attributing anemia to "normal aging" without thorough workup misses treatable causes 5, 7, 8
• Negative RF and ACPA do not exclude progression to RA 1

Treatment Considerations:

• Document predictors of persistent inflammatory arthritis: disease duration ≥6 weeks, morning stiffness >30 minutes, involvement of ≥3 joints, ACPA/RF positivity, and radiographic erosion 1
• These patients require early DMARD therapy even before meeting full RA classification criteria 3