Can you add two slides to the deck: one with the differential diagnosis for an adult presenting with rapid‑onset symmetric polyarthritis, facial burning, temporomandibular (jaw) pain, finger swelling, C‑reactive protein > 270 mg/L, markedly elevated gamma‑glutamyl transferase and alanine aminotransferase, normal blood pressure, mild tachycardia, afebrile status, and no prior medical history; and a second slide explaining why reactive arthritis should be the primary working diagnosis until laboratory results (autoimmune panel, ferritin, viral serologies, HLA‑B27, etc.) return?

Differential Diagnosis for Rapid-Onset Symmetric Polyarthritis with Systemic Inflammation

Primary Differential Considerations

Reactive arthritis should be the leading working diagnosis in this presentation until laboratory results definitively exclude it, given the acute onset, polyarticular involvement, markedly elevated inflammatory markers (CRP >270 mg/L), and hepatic enzyme elevation suggesting systemic inflammation from a recent infection. 1, 2

Key Differential Diagnoses to Consider:

Infectious/Post-Infectious Arthritides:

• Reactive arthritis (ReA) – Most likely given acute onset, polyarthritis, and extreme systemic inflammation; can present with symmetric polyarthritis even in HLA-B27 negative cases 3
• Septic arthritis – Must be excluded urgently despite afebrile status; can present with polyarticular involvement and markedly elevated CRP 4
• Viral arthritis (Parvovirus B19, Hepatitis B/C, HIV) – Can cause symmetric polyarthritis with elevated transaminases 2

Autoimmune/Inflammatory Arthritides:

• Rheumatoid arthritis (RA) – Symmetric small joint involvement is classic, but rapid onset over hours-to-days is atypical; RA typically evolves over weeks-to-months 5
• Adult-onset Still's disease (AOSD) – High spiking fever is typically required (>38.5°C), but this patient is afebrile; however, extreme CRP elevation (>270 mg/L) and hepatic involvement are consistent 4
• Systemic lupus erythematosus (SLE) – Can present with polyarthritis and systemic inflammation 4

Crystal Arthropathies:

• Acute gout – Can present as polyarticular in 10-15% of cases; extreme CRP elevation is consistent 4
• Pseudogout (CPPD) – Less common in younger adults without risk factors 4

Acute Rheumatic Fever:

• Post-streptococcal reactive arthritis – Typically affects large joints with migratory pattern; small joint involvement (fingers) makes this less likely; requires fever >38.5°C and CRP typically >70 mg/L but <270 mg/L 4, 5

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Why Reactive Arthritis is the Primary Working Diagnosis

Clinical Reasoning for Prioritizing Reactive Arthritis

Reactive arthritis must be treated as the primary diagnosis until proven otherwise because it represents the most common cause of acute inflammatory polyarthritis in adults presenting with this constellation of findings, and delayed treatment can result in chronic disability. 2, 6

Supporting Clinical Features:

1. Epidemiology and Presentation Pattern:

• Reactive arthritis is the most common inflammatory polyarthritis in young-to-middle-aged adults presenting acutely 2
• Can occur in both HLA-B27 positive (67%) and HLA-B27 negative (33%) patients 1, 3
• HLA-B27 negative ReA shows more upper extremity and small joint involvement, matching this presentation 3

2. Temporal Profile:

• Rapid onset over hours-to-days is characteristic of reactive arthritis following genitourinary (Chlamydia) or enteric (Salmonella, Shigella, Campylobacter, Yersinia) infection 1, 2
• Symptoms typically develop 1-4 weeks post-infection, which may have been subclinical 6

3. Laboratory Findings:

• Markedly elevated CRP (>270 mg/L) indicates severe systemic inflammation consistent with acute ReA 4
• Elevated GGT and ALT suggest systemic inflammatory response or hepatic involvement, which can occur in reactive arthritis 4
• Afebrile status does not exclude ReA; fever is not required for diagnosis 1, 2

4. Joint Distribution:

• While classic ReA involves asymmetric oligoarthritis of lower extremities, HLA-B27 negative patients frequently present with symmetric polyarthritis and upper extremity involvement 3
• Finger swelling (dactylitis) is a characteristic feature of reactive arthritis 1

5. Extra-Articular Manifestations:

• Facial burning and temporomandibular pain may represent mucocutaneous involvement, which is common in ReA 1
• Mild tachycardia with normal blood pressure suggests systemic inflammation without septic shock 4

Why Other Diagnoses are Less Likely Initially:

Rheumatoid Arthritis:

• RA typically has insidious onset over weeks-to-months, not rapid onset over hours-to-days 5
• While symmetric small joint involvement is classic for RA, the acute presentation and extreme CRP elevation (>270 mg/L) are more consistent with reactive arthritis 5
• RA diagnosis requires positive RF and/or anti-CCP antibodies, which are pending 5

Adult-Onset Still's Disease:

• AOSD typically requires high spiking fever (>38.5°C), which is absent in this patient 4
• While extreme CRP elevation and hepatic involvement are consistent, the absence of fever makes this less likely as the primary diagnosis 4

Acute Rheumatic Fever:

• ARF typically affects large joints (knees, ankles, elbows, wrists) with migratory pattern; small joint involvement of hands is uncommon 4, 5
• Requires fever >38.5°C and evidence of preceding streptococcal infection 4

Septic Arthritis:

• Afebrile status and lack of severe systemic toxicity make bacterial septic arthritis less likely, though it must still be excluded urgently 4
• Polyarticular septic arthritis is rare except in immunocompromised hosts 2

Gout:

• While polyarticular gout can occur, the symmetric distribution and lack of prior episodes make this less likely 4
• Synovial fluid analysis for crystals is essential to exclude this diagnosis 4

Critical Next Steps:

Immediate Actions:

• Synovial fluid aspiration and analysis for crystals, cell count, Gram stain, and culture to exclude septic arthritis and gout 4
• Blood cultures if any concern for bacteremia 4
• Initiate empiric treatment with NSAIDs (if no contraindications) while awaiting laboratory results 2

Pending Laboratory Studies:

• HLA-B27 testing (positive in 67% of ReA cases) 1, 2
• RF, anti-CCP, ANA to evaluate for RA and other autoimmune conditions 4, 5
• Ferritin (markedly elevated >1000 ng/mL suggests AOSD) 4
• Viral serologies (Parvovirus B19, Hepatitis B/C, HIV) 2
• Stool culture and/or urogenital testing for Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia 1, 2
• ASO titer and throat culture for streptococcal infection 4

Treatment Considerations:

• If genitourinary symptoms or recent diarrhea are elicited, consider empiric doxycycline 100 mg twice daily, which may shorten the course of Chlamydia-induced ReA 2
• High-dose NSAIDs (e.g., indomethacin 50 mg three times daily or naproxen 500 mg twice daily) are first-line for symptomatic relief 2
• Intra-articular corticosteroid injection for large joint involvement if symptoms persist 2

Common Pitfalls to Avoid:

• Do not delay synovial fluid analysis – This is essential to exclude septic arthritis and crystal arthropathy, which require different management 4
• Do not assume HLA-B27 negativity excludes ReA – One-third of ReA patients are HLA-B27 negative and may have different joint distribution patterns 3
• Do not wait for fever to diagnose inflammatory arthritis – Afebrile presentation is common in ReA and does not exclude serious pathology 1, 2
• Do not dismiss the diagnosis if initial cultures are negative – Reactive arthritis is defined by sterile synovial fluid with viable but non-culturable bacteria or bacterial antigens in the joint 6