What is the best course of treatment for a 28-year-old adult with a prolonged fever (pyrexia) lasting 15 days, accompanied by symptoms of upper respiratory infection (cold), cough, and arthralgia (joint pain)?

Evaluation and Management of Prolonged Fever with Respiratory and Joint Symptoms

Immediate Diagnostic Approach

This 28-year-old requires urgent evaluation for fever of unknown origin (FUO) and exclusion of serious bacterial infection, particularly community-acquired pneumonia, given the 15-day duration of fever with respiratory symptoms. 1, 2

Critical First Steps

• Obtain a chest X-ray immediately to confirm or exclude pneumonia, as clinical diagnosis alone is insufficient and fever persisting beyond 10-14 days with respiratory symptoms warrants imaging 1, 2
• Assess for pneumonia using clinical criteria: fever >37.8°C, tachycardia >100 bpm, tachypnea >25/min, chest pain, and focal signs on auscultation (crepitations, rales) 1
• In healthy adults under 70 years without all of these findings (tachycardia, tachypnea, fever, abnormal chest exam), pneumonia is unlikely 1

Key Diagnostic Considerations

The 15-day duration of fever exceeds the typical 10-14 day course of viral upper respiratory infection and demands investigation for alternative diagnoses 3, 2:

• Bacterial pneumonia: Most likely if chest X-ray shows infiltrates, particularly given the prolonged fever and cough 1
• Adult-onset Still's disease (AOSD): Consider strongly given the triad of prolonged fever (>95% of cases), arthralgia/arthritis (64-100% of cases), and upper respiratory symptoms including sore throat (35-92% of cases) 1, 4, 5
• Tuberculosis: Must be considered with fever and respiratory symptoms lasting 15 days 2
• Fever of unknown origin (FUO): Defined as fever >38.3°C on multiple occasions for ≥3 weeks without clear diagnosis 6

Laboratory Workup

Obtain the following tests immediately 1:

• Complete blood count: Look for leukocytosis (suggests bacterial infection or AOSD), anemia, thrombocytosis 1
• Inflammatory markers: ESR and CRP (elevated in virtually all AOSD cases) 1
• Ferritin level: Markedly elevated ferritin (>1000 µg/L, often >6000 µg/L) is highly suggestive of AOSD 4, 5
• Liver function tests, creatinine kinase, lactate dehydrogenase: Commonly abnormal in AOSD 1
• Blood cultures (if pneumonia suspected): Collect at least two sets from different sites 1
• Viral testing: Consider respiratory viral panel via NAAT if pneumonia suspected 1

Treatment Algorithm

If Pneumonia is Confirmed on Chest X-ray:

Initiate antibiotic therapy immediately 1:

• For adults <40 years without underlying disease: Oral macrolide (azithromycin or clarithromycin) for suspected atypical pathogens 1
• For adults ≥40 years or with underlying disease: Oral amoxicillin 3 g/day for suspected pneumococcal pneumonia 1
• Alternative regimen: IV co-amoxiclav 1.2 g TDS or cefuroxime 1.5 g TDS plus erythromycin 500 mg QDS or clarithromycin 500 mg BD for severe cases 1

If Pneumonia is Excluded:

Do NOT prescribe antibiotics 1, 3:

• Antibiotics are ineffective for viral respiratory infections and increase adverse effects without benefit 1, 3
• The 15-day duration suggests this is NOT simple viral bronchitis, which resolves within 10-14 days 3, 2

Symptomatic Management:

Provide symptomatic relief while pursuing diagnosis 1, 3, 7:

• Antipyretics: Paracetamol 1000 mg or paracetamol 500 mg/ibuprofen 150 mg combination (the combination is more effective for bacterial fever at 1 hour) 7
• For joint pain: NSAIDs (ibuprofen or naproxen) provide effective relief 1, 3
• For cough: First-generation antihistamines (diphenhydramine) combined with decongestants 1
• Nasal congestion: Oral decongestants (pseudoephedrine/phenylephrine) or nasal saline irrigation 3

When to Suspect Adult-Onset Still's Disease

Consider AOSD if the following features are present 1, 4, 5:

• Fever >38.3°C persisting >15 days with daily or twice-daily spikes 1
• Arthralgia or arthritis (especially wrists, knees, ankles) 1
• Sore throat (68-92% of cases) 1
• Myalgia (56-84% of cases) 1
• Markedly elevated ferritin (>1000 µg/L, often >6000 µg/L) 4, 5
• Leukocytosis with neutrophilia 1, 4
• Elevated inflammatory markers (ESR, CRP) 1
• Salmon-pink evanescent rash (may be absent initially) 1

If AOSD is suspected, initiate high-dose corticosteroids promptly (prednisolone 0.5-1 mg/kg/day), as dramatic response to steroids is characteristic and delays can lead to complications including macrophage activation syndrome 4, 5

Critical Pitfalls to Avoid

• Do not assume all prolonged fever with respiratory symptoms is pneumonia: Absence of infiltrates on chest X-ray should prompt consideration of non-infectious causes 2
• Do not prescribe antibiotics for viral URI: They cause harm without benefit and increase antimicrobial resistance 1, 3
• Do not dismiss purulent sputum as bacterial infection: Discolored mucus reflects inflammation, not bacteria, in viral infections 1, 3
• Do not delay chest X-ray: Clinical diagnosis alone is insufficient for pneumonia 2
• Do not overlook AOSD: Markedly elevated ferritin (>1000 µg/L) in a patient with prolonged fever and arthralgia should trigger immediate consideration of this diagnosis 4, 5

Follow-Up Requirements

• Reassess within 48-72 hours if treated for pneumonia to confirm clinical response 2
• Advise immediate return if symptoms worsen, new symptoms develop (rash, severe joint swelling), or fever persists despite appropriate treatment 2
• Consider hospitalization if severe symptoms, clinical deterioration, inability to maintain oral intake, hypoxemia, or hemodynamic instability occur 2