Systemic Lupus Erythematosus (SLE)
The most likely diagnosis is systemic lupus erythematosus (SLE), based on the constellation of multi-system inflammatory disease with cytopenias, positive ANA at 1:320, serositis (pleural effusion), arthritis, and constitutional symptoms in the appropriate demographic context. 1, 2
Diagnostic Reasoning
Key Features Supporting SLE
Positive ANA at 1:320: This titer exceeds the diagnostic threshold (optimal specificity 86.2% and sensitivity 95.8% for systemic autoimmune rheumatic diseases), making SLE highly likely when combined with clinical features 1
Cytopenias: The patient demonstrates a classic triad of hematologic abnormalities seen in SLE:
Serositis: CT-confirmed pleural effusion with pleuritic chest pain represents serositis, a major criterion for SLE 2
Synovitis of small joints: Symmetric inflammatory arthritis of the hands is characteristic of SLE 2
Constitutional symptoms: Six-month history of fever, weight loss, and arthralgia with markedly elevated inflammatory markers (CRP 99 mg/L, ESR 56 mm/h) 2
Why Not Adult-Onset Still's Disease (AOSD)?
While AOSD was considered, several features argue against it:
Ferritin level: At 920 pg/L, this is elevated but far below the typical range for AOSD. AOSD typically presents with ferritin levels >1000 ng/mL, often exceeding 5000-10,000 ng/mL, and can reach extremely high levels (mean 18,179 ng/mL in AOSD with hemophagocytic syndrome) 4, 5
Absence of characteristic rash: AOSD requires a salmon-pink, evanescent rash on the trunk that appears with fever spikes. This patient has no rash documented 4
Absence of quotidian fever pattern: AOSD characteristically presents with daily fever spikes to ≥39°C. The fever pattern here is not specified as quotidian 4
Positive ANA: While ANA can be positive in AOSD, it is typically negative or low-titer. A titer of 1:320 is more consistent with SLE 4
Cytopenias: The combination of anemia, leukopenia, and thrombocytopenia is more characteristic of SLE than AOSD 2
Why Not Infective Endocarditis?
- Normal heart sounds: No murmurs detected on examination 2
- Normal ECG: Only sinus tachycardia, no conduction abnormalities 2
- Six-month duration: Subacute bacterial endocarditis would typically progress more rapidly or respond to the broad-spectrum antibiotics that would have been tried 2
- Absence of embolic phenomena: No nail fold infarcts, no evidence of septic emboli on imaging 2
- Multi-system autoimmune features: The combination of cytopenias, positive ANA, and serositis points to autoimmune disease rather than infection 2
Critical Next Steps
Immediate confirmatory testing required:
- Anti-dsDNA antibodies: Highly specific for SLE (use Crithidia luciliae immunofluorescence test for highest specificity) 1, 6
- Anti-Smith (Sm) antibodies: Highly specific for SLE with strong confirmatory power 1, 6
- Extractable nuclear antigen (ENA) panel: Including anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La, and anti-Topoisomerase-1 1
- Complement levels (C3, C4): Typically low in active SLE 2
- Urinalysis with microscopy: To evaluate for lupus nephritis (proteinuria, cellular casts) 1
- Direct Coombs test: To evaluate for autoimmune hemolytic anemia 2
Common Pitfalls to Avoid
Do not dismiss SLE based on absence of classic malar rash: Only present in a subset of patients, and photosensitive rashes can be subtle 2
Do not over-rely on ferritin alone: While elevated ferritin can suggest AOSD, the level here (920 pg/L) is insufficient for AOSD diagnosis, and ferritin can be elevated in any inflammatory condition 4
Do not delay specific autoantibody testing: ANA alone is not diagnostic; specific antibodies (anti-dsDNA, anti-Sm) are required for confirmation 1, 6
Do not ignore the prolonged clotting time (7 minutes): This may suggest antiphospholipid antibodies; test for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies 2