What are the differential diagnoses for a middle-aged woman with arthritis, elevated C-Reactive Protein (CRP), and associated hair loss, without a prior history of autoimmune diseases?

Differential Diagnoses for Arthritis with Elevated CRP and Hair Loss

In a middle-aged woman presenting with arthritis, elevated CRP, and hair loss, systemic lupus erythematosus (SLE) should be the primary consideration, followed by seronegative rheumatoid arthritis, psoriatic arthritis, and dermatomyositis. 1

Primary Autoimmune Differential Diagnoses

Systemic Lupus Erythematosus (Most Likely)

• SLE frequently presents with both scarring and non-scarring alopecia alongside inflammatory arthritis and elevated acute phase reactants 2
• Non-scarring alopecia is a hallmark finding in acute systemic lupus erythematosus, while scarring alopecia develops when discoid lesions involve the scalp 2
• The combination of polyarthritis, elevated CRP, and hair loss in a middle-aged woman strongly suggests SLE as the leading diagnosis 1, 2
• Order ANA, anti-dsDNA, anti-Smith antibodies, complement levels (C3, C4), and complete blood count to evaluate for SLE 1, 3

Seronegative Rheumatoid Arthritis

• Seronegative RA accounts for 20-30% of RA cases and can present with elevated CRP and polyarticular involvement 4, 3
• While hair loss is not a classic feature of RA, systemic inflammation can cause telogen effluvium 5
• Test for RF and anti-CCP antibodies (both may be negative), and obtain bilateral hand, wrist, and foot X-rays to assess for characteristic erosions 1, 4, 3
• Look for symmetric involvement of small joints (MCPs, PIPs, wrists, MTPs) with morning stiffness >30 minutes 1, 4, 6

Psoriatic Arthritis

• PsA can present with elevated CRP, polyarticular involvement, and is associated with scalp psoriasis that may cause hair loss 1, 7
• Elevated CRP at first presentation predicts more severe, erosive PsA with higher treatment resistance 7
• Examine carefully for psoriatic plaques, nail dystrophy (pitting, onycholysis), dactylitis, and enthesitis 1, 6
• Consider HLA-B27 testing if axial or entheseal involvement is present 1, 3

Dermatomyositis

• Dermatomyositis presents with non-scarring, generalized alopecia alongside inflammatory arthritis and elevated CRP 2
• Look for characteristic heliotrope rash, Gottron's papules, proximal muscle weakness, and elevated creatine kinase 1, 2
• Order creatine kinase, aldolase, myositis-specific antibodies (anti-Jo-1, anti-Mi-2), and consider EMG or muscle biopsy if weakness is present 1

Secondary Considerations

Sarcoidosis

• Osseous sarcoidosis can present with arthritis, elevated inflammatory markers, and alopecia in affected scalp areas 1
• Consider chest X-ray, serum ACE levels, and tissue biopsy if granulomatous disease is suspected 1

Spondyloarthropathies

• Axial spondyloarthritis and reactive arthritis can present with elevated CRP and inflammatory arthritis 1
• Hair loss is not typical but may occur with severe systemic inflammation 5
• Assess for inflammatory back pain, sacroiliitis, enthesitis, uveitis, and inflammatory bowel disease 1

Essential Diagnostic Workup

Immediate Laboratory Testing

• ESR and CRP for baseline inflammatory marker assessment 1, 3, 6
• RF and anti-CCP antibodies (predictive for RA despite potential seronegativity) 1, 4, 3, 6
• ANA with reflex to ENA panel (anti-dsDNA, anti-Smith, anti-Ro, anti-La) to evaluate for SLE and other connective tissue diseases 1, 4, 3
• Complete blood count with differential (assess for cytopenias common in SLE) 4, 3, 6
• Comprehensive metabolic panel including liver and renal function 4, 3, 6
• Complement levels (C3, C4) if SLE is suspected 1
• Creatine kinase if muscle involvement or dermatomyositis is suspected 1, 2
• Urinalysis to screen for renal involvement 1, 4, 3, 6

Imaging Studies

• Bilateral hand, wrist, and foot X-rays at baseline to assess for erosions (predictive of RA and disease persistence) 1, 4, 3, 6
• Consider ultrasound with Power Doppler or MRI if clinical synovitis is subtle but suspicion remains high 1, 4, 6
• MRI is more sensitive than ultrasound for detecting bone marrow edema, the best predictor of disease progression 4, 6

Clinical Examination Priorities

• Perform 28-joint count examination assessing PIPs, MCPs, wrists, elbows, shoulders, and knees for tenderness and swelling 1, 4, 3, 6
• Document joint distribution pattern (symmetric vs asymmetric), morning stiffness duration, and functional limitations 1, 6
• Examine scalp for scarring vs non-scarring alopecia, psoriatic plaques, and discoid lesions 1, 2
• Assess for malar rash, photosensitivity, oral ulcers, Raynaud's phenomenon, and muscle weakness 2
• Examine skin for psoriatic plaques, nail changes, and dermatomyositis-specific rashes 1, 2

Critical Clinical Pearls

• Do not dismiss inflammatory arthritis based on normal ESR/CRP alone—40-50% of patients with active RA have normal acute phase reactants 4, 3
• Hair loss in autoimmune disease can be either scarring (discoid lupus, morphea) or non-scarring (acute SLE, dermatomyositis, telogen effluvium from systemic inflammation) 2, 5
• Seronegative disease (negative RF and anti-CCP) does not exclude RA and carries similar prognosis to seropositive disease 4, 3
• Refer to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected, as early treatment prevents irreversible joint damage 4, 3, 6
• The combination of arthritis, elevated CRP, and hair loss mandates evaluation for systemic autoimmune disease rather than isolated joint disease 1, 2