What is the most likely diagnosis for a patient presenting with arthralgia, fever, weight loss, pleuritic chest pains, synovitis, anemia (low Hemoglobin (Hb)), leukopenia (low White Blood Cell (WBC) count), thrombocytopenia (low Platelet count), elevated C-reactive protein (CRP), elevated Erythrocyte Sedimentation Rate (ESR), and a positive Antinuclear Antibody (ANA) test?

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Systemic Lupus Erythematosus (SLE)

The most likely diagnosis is Systemic Lupus Erythematosus (C), based on the constellation of multi-system involvement with arthralgia, fever, weight loss, pleuritic chest pain, synovitis, cytopenias (anemia, leukopenia, thrombocytopenia), elevated inflammatory markers, and a strongly positive ANA at 1:320. 1

Diagnostic Reasoning

Why SLE is the Correct Diagnosis

The patient fulfills multiple diagnostic criteria for SLE with characteristic laboratory and clinical features:

  • Positive ANA at 1:320 exceeds the diagnostic threshold and makes SLE highly likely when combined with clinical features, with specificity of 86.2% and sensitivity of 95.8% for systemic autoimmune rheumatic diseases 1

  • Cytopenias are characteristic of SLE: The patient demonstrates anemia (Hb 89 g/L), leukopenia (WBC 3.2 x 10⁹/L), and thrombocytopenia (platelet count 99 x 10⁹/L), which are hallmark features 1, 2

  • Multi-system involvement affecting at least two organ systems (musculoskeletal with arthralgia and synovitis, pulmonary with pleuritic chest pain and pleural effusion) strongly suggests SLE 3

  • Serositis is evident with pleuritic chest pain and confirmed small left pleural effusion on CT, which is a classic SLE manifestation 2

  • Inflammatory markers show elevated CRP (99 mg/L) and ESR (56 mm/h), consistent with active systemic inflammation 2

  • Lymphopenia (17% vs normal 20-40%) is specifically associated with SLE and increases infection risk 2

Why Adult-Onset Still's Disease (AOSD) is Unlikely

Several key features argue strongly against AOSD:

  • Ferritin level of 920 pg/L is elevated but far below the typical range for AOSD, which characteristically presents with ferritin levels >1000 ng/mL and often >5000 ng/mL 1, 2

  • Absence of the characteristic salmon-pink, evanescent rash that occurs in 51-87% of AOSD patients and typically appears with fever spikes 2

  • No quotidian fever pattern (daily spiking fevers) that is pathognomonic for AOSD 2

  • Absence of sore throat (reported in 38-92% of AOSD cases) 2

  • The strongly positive ANA at 1:320 is atypical for AOSD, where ANAs are typically negative or low-titer 2

Why Infective Endocarditis is Unlikely

Clinical and laboratory features exclude endocarditis:

  • Normal heart sounds on examination with no murmurs 2

  • Absence of nail fold infarcts (splinter hemorrhages) which would suggest septic emboli 2

  • No evidence of vegetation or valvular abnormality mentioned in the clinical assessment 2

  • The pattern of cytopenias and positive ANA points to autoimmune disease rather than infection 1

Critical Diagnostic Pitfalls to Avoid

Do not rely solely on ferritin levels in this context: Ferritin is an acute phase reactant and can be falsely elevated in lupus cases, but the level here (920 pg/L) is insufficient for AOSD diagnosis 4, 1

Do not dismiss SLE based on absence of rash: The patient lacks the classic malar rash, but SLE should be suspected in any patient with unexplained disease involving two or more organ systems, even without typical cutaneous manifestations 3

Recognize that CRP elevation in SLE warrants attention: While many authors report that SLE patients rarely have significantly elevated CRP, values >50 mg/L should prompt evaluation for superimposed infection, though this patient's CRP of 99 mg/L in the context of active multi-system disease is consistent with lupus serositis 2

Next Diagnostic Steps Required

Further serological testing should include:

  • Anti-dsDNA antibodies using Crithidia luciliae immunofluorescence test for highest specificity 1

  • Anti-Smith (Sm) antibodies, which are highly specific for SLE with strong confirmatory power 1

  • Urinalysis with microscopy to evaluate for lupus nephritis (proteinuria, cellular casts), as renal involvement may be asymptomatic 2, 1

  • Complement levels (C3, C4) which are often low in active SLE 2

References

Guideline

Systemic Lupus Erythematosus Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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