What is the likely diagnosis for a patient with leukocytosis and cough?

Leukocytosis with Cough: Likely Diagnosis and Management

The most likely diagnosis for a patient presenting with a white blood cell count of 17,000/μL and cough is bacterial pneumonia or acute bronchitis, though pertussis infection must be strongly considered if the cough has lasted ≥2 weeks with paroxysmal features. 1, 2

Immediate Diagnostic Approach

Assess vital signs immediately to identify fever ≥38°C, heart rate ≥100 beats/min, or respiratory rate ≥24 breaths/min, which suggest bacterial pneumonia requiring urgent chest radiography. 2

Physical Examination Priorities

• Listen for asymmetrical lung sounds, focal consolidation, rales, egophony, or increased fremitus that indicate pneumonia requiring imaging. 2
• Examine for upper airway findings including rhinorrhea, postnasal drainage, pharyngeal erythema, or swollen turbinates suggesting upper respiratory infection or postinfectious cough. 1
• Obtain chest X-ray if vital signs are abnormal, focal lung findings are present, or the patient appears systemically ill. 2

Key Differential Diagnoses by Clinical Context

Acute Bacterial Pneumonia (Most Common with Leukocytosis + Cough)

Bacterial pneumonia is the primary consideration when leukocytosis accompanies cough with fever, focal lung findings, or systemic symptoms. 3 The peripheral white blood cell count can double within hours in response to bacterial infection due to large bone marrow storage pools of neutrophils. 3

Pertussis Infection (Critical to Exclude)

Suspect pertussis when cough lasts ≥2 weeks and is accompanied by paroxysms of coughing, post-tussive vomiting, or an inspiratory whooping sound. 1, 2

• Leukocytosis with lymphocytosis is characteristic of pertussis, though this finding is frequently absent in adults. 1
• Obtain nasopharyngeal aspirate or Dacron swab for culture to confirm diagnosis, as isolation of Bordetella pertussis is the only certain diagnostic method. 1, 2
• Order paired acute and convalescent sera for fourfold increase in IgG or IgA antibodies to pertussis toxin if culture is negative but clinical suspicion remains high. 1, 2
• Initiate macrolide antibiotic within the first few weeks to diminish coughing paroxysms and prevent transmission if pertussis is confirmed. 1, 2
• Note that extreme leukocytosis (>100 × 10⁹/L) in pertussis is an independent predictor of mortality in severe cases, particularly in infants. 4

Postinfectious Cough (If Preceded by URI)

Postinfectious cough should be considered when cough follows an obvious respiratory infection, lasts 3-8 weeks, and occurs without vital sign abnormalities or focal lung findings. 5, 2

• Leukocytosis in this context typically reflects the preceding infection rather than ongoing bacterial disease. 1, 5
• Antibiotics are explicitly contraindicated for postinfectious cough unless there is clear evidence of bacterial sinusitis or early pertussis infection. 5
• First-line treatment is inhaled ipratropium bromide 2-3 puffs four times daily, which has the strongest evidence for attenuating symptoms. 6, 5

Tuberculosis (In High-Risk Patients)

Screen for TB risk factors including origin from high TB prevalence areas, HIV infection, homelessness, incarceration, or healthcare work. 2

• Obtain chest radiograph and sputum smears/cultures for acid-fast bacilli if risk factors are present or cough persists >3 weeks with systemic symptoms. 2
• Consider TB even in low-prevalence areas when common causes have been ruled out and cough remains unexplained. 2

Critical Red Flags Requiring Immediate Investigation

Obtain chest radiography immediately if any of the following are present: 6, 2

• Hemoptysis
• Significant unintentional weight loss
• Voice changes or hoarseness
• Asymmetrical lung sounds or focal consolidation
• Vital sign abnormalities

Medication Review

Assess for ACE inhibitor use, which causes persistent cough in a significant percentage of patients and can be associated with mild leukocytosis from chronic inflammation. 2, 3

• Stop the ACE inhibitor if present, with median time to cough resolution of 26 days. 2

Common Pitfalls to Avoid

Do not prescribe antibiotics reflexively based on leukocytosis and cough alone without evidence of bacterial infection, as most post-viral coughs produce colored sputum without bacterial infection. 6, 5

Do not assume leukocytosis always indicates infection—nonmalignant causes include medications, smoking, obesity, chronic inflammatory conditions, surgery, exercise, trauma, and emotional stress. 3

Do not overlook pertussis in adults, as the classic whooping sound is usually absent and the presentation may be a nondistinct protracted cough. 1

Do not fail to consider immunocompromised status, as patients with prolonged neutropenia are predisposed to bacterial sinus and lung infections as well as invasive fungal infections. 1

When to Refer or Escalate

Refer to hematology/oncology if malignancy cannot be excluded based on fever, weight loss, bruising, fatigue, or persistent unexplained leukocytosis without infectious etiology. 3

Consider infectious disease consultation for persistent leukocytosis without clear source, as this constitutes 4.5% of ID consults and may represent persistent inflammation-immunosuppression and catabolism syndrome (PICS). 7