In a 53-year-old woman with six months of fever, weight loss, arthralgia and small‑joint synovitis, recent pleuritic chest pain and a small left pleural effusion, no rash or nail‑fold infarcts, normal heart sounds and sinus tachycardia, which diagnosis is most likely: infective endocarditis, adult‑onset Still’s disease, systemic lupus erythematosus, or rheumatoid arthritis with vasculitis?

Systemic Lupus Erythematosus

The most likely diagnosis is systemic lupus erythematosus (C). This 53-year-old woman presents with a 6-month history of constitutional symptoms (fever, weight loss), small-joint synovitis, arthralgia, and serositis (pleuritic chest pain with pleural effusion)—a constellation that strongly suggests SLE rather than the other options.

Diagnostic Reasoning

Why SLE Is Most Likely

• Pericardial and pleural involvement occurs commonly in SLE, affecting approximately 5–15% of patients with systemic autoimmune diseases who develop pericarditis, and SLE is specifically listed among the most common autoimmune causes of serositis 1

• Small-joint synovitis with arthralgia is a cardinal feature of SLE, and when combined with constitutional symptoms and serositis, this pattern strongly suggests lupus 2, 3

• The 6-month duration with progressive multisystem involvement (musculoskeletal, constitutional, and serosal) fits the typical presentation of SLE, where diagnosis requires evidence of involvement in at least two organ systems 3

• Pleural effusion without pulmonary embolism or consolidation is characteristic of lupus pleuritis, which represents inflammatory serositis rather than infection or thromboembolism 1

Why the Other Diagnoses Are Less Likely

Infective endocarditis (A) is unlikely because:

• Heart sounds are normal—no murmur is documented 1
• Blood cultures would be expected to be mentioned if obtained, and the 6-month chronic course without hemodynamic compromise argues against active endocarditis 1
• The absence of nail-fold infarcts (which would suggest septic emboli) further reduces this probability 1

Adult-onset Still's disease (B) is less likely because:

• The classic salmon-pink evanescent rash is absent, which is present in >85% of AOSD cases and is a major diagnostic criterion 1, 4
• While AOSD can present with fever, arthralgia, and serositis, the absence of the characteristic rash, sore throat, and marked leukocytosis (not mentioned here) makes this diagnosis less probable 1, 5
• AOSD typically presents with very high ferritin levels (>5× normal) and elevated IL-18, which are key diagnostic biomarkers not mentioned in this case 1

Rheumatoid arthritis with vasculitis (D) is unlikely because:

• RA vasculitis typically occurs in long-standing, severe, seropositive RA (usually >10 years of disease) and would be expected to show nail-fold infarcts, digital ischemia, or cutaneous ulceration—none of which are present 6
• The absence of nail-fold infarcts specifically argues against vasculitis as a complicating feature 6
• The pleural effusion in RA is typically a late manifestation in established disease, not a presenting feature in a patient without prior RA diagnosis 6

Recommended Diagnostic Workup

Obtain comprehensive autoimmune serology immediately:

• Antinuclear antibody (ANA) with titer and pattern—this is the primary screening test for SLE 3
• If ANA is positive (≥1:40), proceed with anti-double-stranded DNA (anti-dsDNA) and anti-Smith antibodies, which are highly specific for SLE 3
• Complement levels (C3, C4)—low levels suggest active lupus with immune complex consumption 1
• Complete blood count to assess for cytopenias (anemia, leukopenia, thrombocytopenia), which are common in SLE 2

Assess for renal involvement:

• Urinalysis with microscopy looking for proteinuria, hematuria, or cellular casts 1, 2
• Serum creatinine and estimated glomerular filtration rate 1

Apply the American College of Rheumatology classification criteria:

• If ≥4 of 11 criteria are met, SLE can be diagnosed with 95% specificity and 85% sensitivity 2, 3
• This patient already demonstrates: (1) arthritis, (2) serositis (pleuritis), and (3) constitutional symptoms—three criteria are already evident clinically 2, 3

Critical Diagnostic Pitfall

Do not dismiss the diagnosis if ANA is negative. While rare, ANA-negative SLE exists in patients with persistent characteristic multisystem involvement, and such patients should still be evaluated with anti-dsDNA and anti-Sm antibodies 3. However, an ANA titer <1:40 makes SLE much less likely unless there is overwhelming clinical evidence 3.

Initial Management Pending Confirmation

• Refer to rheumatology urgently for patients with suspected SLE and multisystem involvement, as early diagnosis and treatment reduce morbidity and mortality 2

• Hydroxychloroquine is the cornerstone of SLE treatment and reduces disease flares and constitutional symptoms; it should be initiated once the diagnosis is confirmed 2

• Low-dose glucocorticoids (e.g., prednisone ≤10 mg/day) can be used to treat most manifestations while awaiting rheumatology evaluation 2

• Monitor for organ damage (especially renal) every 3 months during the first 2–3 years, as this is when lupus nephritis most commonly develops 1