What is the most likely diagnosis for a female patient presenting with arthralgia, fever, weight loss, pleuritic chest pain, and synovitis, with lab results showing anemia, leukopenia, thrombocytopenia, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and a high antinuclear antibody (ANA) titer, and a pulmonary angiography CT confirming a small left pleural effusion?

Systemic Lupus Erythematosus (SLE)

The most likely diagnosis is C. Systemic lupus erythematosus (SLE), based on the constellation of multi-system involvement (arthralgia, fever, weight loss, pleuritic chest pain, synovitis), characteristic laboratory findings (pancytopenia, elevated inflammatory markers, high ANA titer 1:320), and pleural effusion in a female patient.

Clinical Reasoning for SLE Diagnosis

This patient presents with classic features that strongly support SLE over the other differential diagnoses:

Multi-System Involvement Consistent with SLE

• Musculoskeletal manifestations: Arthralgia and synovitis of small joints of the hands are common in SLE, affecting the majority of patients 1
• Constitutional symptoms: The 6-month history of fever, weight loss, and malaise represents the systemic inflammatory nature of SLE 1
• Serositis: Pleuritic chest pain with confirmed small left pleural effusion on CT is a characteristic feature, as up to 50% of SLE patients develop pleural disease during their illness 2

Laboratory Profile Strongly Supports SLE

• Hematologic abnormalities: The pancytopenia (anemia Hb 89, leukopenia WBC 3.2, thrombocytopenia platelets 99) is highly characteristic of SLE 2

  • Severe anemia, thrombocytopenia, and leucopenia have been variably associated with organ involvement, disease progression, and worse prognosis in SLE 2
  • Thrombocytopenia in SLE patients is associated with renal disease, higher disease activity, more end organ damage, and higher mortality 3
  • The combination of all three cytopenias (anemia, leukopenia, thrombocytopenia) is particularly suggestive of immune-mediated destruction in SLE 4, 5

• Inflammatory markers: Markedly elevated CRP (99 mg/L) and ESR (56 mm/h) indicate active systemic inflammation 2

  • While many authors report that SLE patients rarely have elevated CRP levels, significant increases can occur with active disease 2
  • The elevated ferritin (920 pg/L) reflects the acute phase response and systemic inflammation 2

• Autoantibody profile: ANA titer of 1:320 is significantly elevated and highly supportive of SLE diagnosis 1

  • The 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria include ANA positivity as a key immunologic measure for SLE 1

Why Not the Other Diagnoses?

Infective Endocarditis (Option A) - Unlikely

• Normal heart sounds on examination argue strongly against endocarditis 2
• No mention of cardiac murmurs, which would be expected in infective endocarditis
• No nail fold infarcts (splinter hemorrhages), which are characteristic of endocarditis
• While fever and elevated inflammatory markers occur in endocarditis, the multi-system autoimmune features, high ANA titer, and pancytopenia are not typical 2

Adult-Onset Still's Disease (Option B) - Less Likely

• Adult-onset Still's disease typically presents with very high spiking fevers (often >39°C with quotidian pattern), which is not specifically described here 2
• The characteristic salmon-pink evanescent rash of Still's disease is notably absent in this patient 2
• While Still's disease can cause arthritis, elevated inflammatory markers, and serositis, the high ANA titer (1:320) is atypical for Still's disease 2
• The pancytopenia pattern (all three cell lines affected) is more characteristic of SLE than Still's disease 3, 4

Clinical Implications and Prognosis

This patient requires urgent rheumatology consultation and initiation of hydroxychloroquine as standard of care, which has been associated with significant reduction in mortality in SLE 1:

• The presence of thrombocytopenia indicates higher disease activity and more probability of end organ damage 3
• The pleural effusion and constitutional symptoms suggest active multi-system disease requiring immunosuppressive therapy beyond hydroxychloroquine 1
• Additional immunosuppressive agents such as azathioprine, mycophenolate mofetil, or cyclophosphamide should be considered for moderate to severe disease 1
• The patient should be monitored for lupus nephritis development, as approximately 40% of SLE patients develop this complication 1

Monitoring Requirements

• Serial monitoring of complement levels (C3, C4) and anti-dsDNA antibodies to assess disease activity 2
• Regular assessment of serum creatinine, urinalysis, and urine protein/creatinine ratio to detect early renal involvement 2
• Follow-up complete blood counts to monitor cytopenias, as severe leucopenia and lymphopenia are associated with increased infection risk 2