What are the differential diagnoses for an 18‑year‑old woman with a 10‑day history of fever, dry cough, loss of appetite and weight loss, a normal total leukocyte count (~8000/µL), a negative Cartridge Based Nucleic Acid Amplification Test (CBNAAT) on sputum, and a chest X‑ray showing dense consolidation in the right upper lobe?

Differential Diagnosis for Young Female with Dense Right Upper Lobe Consolidation and Negative CBNAAT

Despite the negative CBNAAT, pulmonary tuberculosis remains the leading differential diagnosis in this 18-year-old woman with a 10-day history of fever, dry cough, weight loss, appetite loss, normal leukocyte count, and dense right upper lobe consolidation—and empiric anti-tuberculosis therapy should be strongly considered while pursuing additional diagnostic workup. 1

Primary Differential Diagnoses

1. Pulmonary Tuberculosis (Most Likely)

• Classic presentation: The combination of prolonged fever, dry cough, weight loss, loss of appetite over 10 days with upper lobe consolidation is highly characteristic of TB, even with negative CBNAAT 2, 1
• CBNAAT limitations: A single negative CBNAAT does not exclude TB—sensitivity ranges from 70-90% depending on bacillary load, and paucibacillary disease (common in young females) frequently produces false negatives 1
• Normal WBC count: TB characteristically presents with normal or only mildly elevated leukocyte counts, distinguishing it from bacterial pneumonia 2, 3
• Upper lobe predilection: Dense right upper lobe consolidation is the classic radiographic finding for reactivation TB in immunocompetent adults 2
• Constitutional symptoms: The triad of fever, night sweats, and weight loss over 10 days strongly suggests TB rather than typical bacterial pneumonia 2, 1

Next steps for TB workup:

• Obtain at least three early-morning sputum samples for AFB smear and mycobacterial culture 1
• Repeat CBNAAT on additional sputum specimens 1
• Consider bronchoscopy with BAL and transbronchial biopsy if sputum cannot be obtained 1
• Initiate empiric four-drug anti-TB therapy (isoniazid, rifampin, pyrazinamide, ethambutol) immediately given high clinical suspicion in a young patient with classic presentation 1

2. Mycoplasma Pneumonia

• Atypical presentation: Mycoplasma pneumoniae commonly affects young adults and school-aged individuals, presenting with fever, headaches, arthralgias, and progressive dry cough 4
• Normal WBC: Mycoplasma typically presents with normal or decreased leukocyte counts, consistent with this patient 2, 4
• Radiographic findings: Can show reticular shadows, small patchy infiltrates, or consolidations that may mimic TB 2
• Diagnostic challenge: Diagnosis is often made retrospectively by serology (Mycoplasma-specific IgM), limiting early diagnosis 2, 4

Distinguishing features:

• Mycoplasma usually has a more gradual onset and less prominent constitutional symptoms (weight loss, appetite loss) compared to this patient 4
• Upper lobe consolidation is less typical for Mycoplasma 2

3. Bacterial Pneumonia (Less Likely)

• Against bacterial etiology:
  • Normal WBC count (8,000/µL) argues strongly against typical bacterial pneumonia, which usually presents with leukocytosis >11,000/µL 5, 3
  • Predominantly dry cough rather than productive purulent sputum 5
  • 10-day duration without clinical deterioration is atypical for untreated bacterial pneumonia 5
• If considered: Would expect Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus with high fever and moist rales 2, 5

4. Viral Pneumonia (Including COVID-19)

• Possible but less likely:
  • COVID-19 and other viral pneumonias typically show bilateral, multi-lobar involvement rather than isolated dense upper lobe consolidation 2
  • Normal or decreased leukocyte count is consistent with viral infection 2
  • Dry cough and fever fit viral etiology 2
• Against viral etiology: Unilateral dense upper lobe consolidation is atypical; viral pneumonias usually show ground-glass opacities and bilateral patchy infiltrates 2

5. Fungal Infection (Consider if Immunocompromised)

• Allergic Bronchopulmonary Aspergillosis (ABPA): Would require underlying asthma, elevated IgE >417 IU/L, and typically shows central bronchiectasis rather than dense consolidation 2
• Other fungal pneumonias: Less likely without immunocompromise or specific exposures 2

6. Malignancy (Unlikely but Must Exclude)

• Bronchogenic carcinoma or lymphoma: Can present with cough, weight loss, and upper lobe mass, but 10-day duration is too short for primary malignancy 2
• Consider if: Symptoms persist despite appropriate antimicrobial therapy; follow-up chest imaging at 6 weeks is essential 5

Critical Diagnostic Algorithm

Immediate actions:

1. Obtain three early-morning sputum samples for AFB smear, mycobacterial culture, and repeat CBNAAT 1
2. Check inflammatory markers: CRP and ESR (likely elevated in TB) 3, 6
3. HIV testing: Mandatory in all TB suspects 1
4. Mycoplasma serology: IgM antibodies 2, 4
5. Blood cultures: Two sets to exclude bacteremia 5

If sputum cannot be obtained:

• Bronchoscopy with BAL and transbronchial biopsy for AFB smear, culture, CBNAAT, and histopathology 1, 7
• EBUS-TBNA of mediastinal lymph nodes if enlarged on imaging 7

Empiric treatment decision:

• Initiate four-drug anti-TB therapy immediately (isoniazid, rifampin, pyrazinamide, ethambutol) given high clinical suspicion, classic presentation, and upper lobe consolidation—do not wait for culture confirmation 1
• Add azithromycin 500 mg daily to cover atypical pathogens including Mycoplasma while awaiting serology 4, 5

Common Pitfalls to Avoid

• Do not rely on single negative CBNAAT to exclude TB in a patient with classic clinical and radiographic features 1
• Do not delay empiric anti-TB therapy while awaiting culture results in high-risk presentations—cultures take 4-8 weeks and treatment delay worsens outcomes 1
• Do not assume bacterial pneumonia based solely on consolidation when WBC is normal and cough is dry 5, 3
• Do not forget HIV testing—immunocompromised patients may have atypical presentations and require modified treatment 1
• Do not overlook Mycoplasma in young adults with prolonged dry cough and normal WBC, even with upper lobe involvement 2, 4

Follow-Up Imaging

• Repeat chest X-ray at 6 weeks if symptoms persist or to confirm resolution and exclude underlying malignancy 5
• CT chest if initial radiograph findings are equivocal or if clinical response to therapy is poor 2, 1