Systemic Lupus Erythematosus
The most likely diagnosis is C. Systemic lupus erythematosus (SLE). This patient presents with a classic constellation of features that strongly support SLE: positive ANA at 1:320 (well above the diagnostic threshold), cytopenias (anemia, leukopenia, thrombocytopenia), serositis (pleural effusion with pleuritic chest pain), inflammatory arthritis of small joints, constitutional symptoms, and markedly elevated inflammatory markers 1.
Diagnostic Reasoning
Why SLE is the Correct Diagnosis
The ANA titer of 1:320 is highly significant. This exceeds the diagnostic threshold and, when combined with the clinical features present, makes SLE highly likely with a specificity of 86.2% and sensitivity of 95.8% for systemic autoimmune rheumatic diseases 1.
The cytopenias are characteristic of SLE:
- Anemia (Hb 89 g/L, normal 120-160 g/L) 2
- Leukopenia (WBC 3.2 x 10⁹/L, normal 4-10.5 x 10⁹/L) 2
- Thrombocytopenia (platelets 99 x 10⁹/L, normal 150-400 x 10⁹/L) 2
These hematologic abnormalities are strongly associated with SLE, with severe anemia and thrombocytopenia linked to organ involvement, disease progression, and worse prognosis 2.
The serositis (pleural effusion with pleuritic chest pain) is a major manifestation of SLE and fits perfectly with the clinical picture 1.
The inflammatory arthritis affecting small joints of the hands with synovitis is a common SLE manifestation 1.
Why Adult-Onset Still's Disease is Unlikely
The ferritin level of 920 pg/L argues strongly against AOSD. While elevated, this is far below the typical range for AOSD, which characteristically presents with ferritin levels >1000 ng/mL, often exceeding 5000 ng/mL 1.
The absence of the characteristic salmon-pink, evanescent rash on the trunk is notable, as this is a hallmark feature of AOSD 2, 1.
The fever pattern is not described as quotidian (daily spiking fever), which is typical of AOSD 2, 1.
The markedly positive ANA (1:320) is unusual for AOSD. While AOSD can occasionally have positive ANA, high titers are more characteristic of connective tissue diseases like SLE 2.
Why Infective Endocarditis is Unlikely
Normal heart sounds on examination make infective endocarditis less likely 2.
The absence of nail fold infarcts, which would suggest embolic phenomena, argues against endocarditis 2.
The 6-month duration with constitutional symptoms, arthritis, and positive ANA points toward a systemic autoimmune disease rather than infection 1.
Important Caveat Regarding CRP in SLE
**The markedly elevated CRP (99 mg/L, normal <8.2 mg/L) requires careful interpretation.** The European League Against Rheumatism notes that patients with SLE rarely have elevated CRP levels, and when CRP is significantly increased (>50 mg/L), a superimposed infection should be excluded 2, 3. However, this patient has been unwell for 6 months with progressive symptoms, making acute infection less likely as the primary diagnosis, though it should still be considered as a complicating factor.
The discordance between very high CRP and moderately elevated ESR (56 mm/h) is noteworthy. Research shows that high CRP/low ESR discordance occurs more commonly with infections, while high ESR/low CRP discordance is more common in connective tissue diseases like SLE 4. This patient has both elevated, but the CRP is disproportionately high, warranting infection workup even as SLE remains the primary diagnosis.
Next Steps in Management
Confirm the diagnosis with additional specific autoantibody testing:
- Anti-dsDNA antibodies (highly specific for SLE) using Crithidia luciliae immunofluorescence test 1
- Anti-Smith (Sm) antibodies (highly specific for SLE with strong confirmatory power) 1
Evaluate for lupus nephritis immediately:
- Urinalysis with microscopy to assess for proteinuria and cellular casts 1
- Serum creatinine and urine protein/creatinine ratio 2
Rule out superimposed infection given the markedly elevated CRP, particularly before initiating immunosuppressive therapy 2, 3.