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 positive ANA at 1:320 exceeds the diagnostic threshold for SLE 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 This patient demonstrates the classic multi-system involvement pattern of SLE:

  • Hematologic abnormalities: The patient has anemia (Hb 89 g/L), leukopenia (WBC 3.2 x 10⁹/L), and thrombocytopenia (platelet count 99 x 10⁹/L)—all three cytopenias are characteristic of SLE 1, 2

  • Musculoskeletal involvement: Arthralgia and synovitis of small joints of the hands are common early manifestations of SLE 3

  • Serositis: Pleuritic chest pain with confirmed pleural effusion on CT represents serositis, a classic SLE manifestation 3

  • Constitutional symptoms: The 6-month history of fever, weight loss, and malaise fits the typical insidious presentation of SLE 3

  • Inflammatory markers: Elevated CRP (99 mg/L) and ESR (56 mm/h) are consistent with active SLE, though CRP elevation can be variable in SLE 2

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

The ferritin level of 920 pg/L, while elevated, falls far below the typical range for AOSD, which characteristically presents with ferritin levels >1000 ng/mL and often exceeds 3000-5000 ng/mL. 1, 2 Additional features arguing against AOSD include:

  • Absence of characteristic rash: AOSD typically presents with a salmon-pink, evanescent rash on the trunk and extremities that appears with fever spikes, which is absent in this patient 2

  • Fever pattern: AOSD characteristically shows quotidian (daily) fever spikes, often reaching 39-40°C, which is not described here 2

  • Leukocytosis pattern: AOSD typically presents with marked leukocytosis (often >15 x 10⁹/L with neutrophilia >80%), whereas this patient has leukopenia 2

  • Sore throat: A prominent sore throat occurs in 68-92% of AOSD cases but is not mentioned here 2

Why Infective Endocarditis is Unlikely

  • Normal heart sounds: The examination reveals normal heart sounds with no murmurs, making endocarditis unlikely 1

  • Hematologic pattern: Infective endocarditis does not typically cause the combination of leukopenia and thrombocytopenia seen here; it usually causes leukocytosis 1

  • Multi-system autoimmune features: The positive ANA at high titer and the specific pattern of cytopenias point toward autoimmune disease rather than infection 1, 4

Next Diagnostic Steps

To confirm SLE diagnosis, the following specific autoantibody testing should be performed:

  • Anti-dsDNA antibodies using Crithidia luciliae immunofluorescence test for highest specificity 1, 2

  • Anti-Smith (Sm) antibodies, which are highly specific for SLE with strong confirmatory power 1, 3

  • Complement levels (C3, C4): Hypocomplementemia supports active SLE 2, 3

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

Critical Clinical Pitfall

A common diagnostic error is waiting for all "classic" SLE features before making the diagnosis. SLE should be suspected in any patient with unexplained disease involving two or more organ systems, even without the classic malar rash 5, 6. In this case, the absence of rash should not delay diagnosis, as mucocutaneous manifestations may not be present initially 3, 5. Early diagnosis and treatment are essential to prevent irreversible organ damage, particularly renal involvement which can progress silently 2, 1.

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

Research

Systemic lupus erythematosus.

Lancet (London, England), 2024

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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