What are the next steps for an elderly male patient with asthma, leukocytosis, and an elevated absolute lymphocyte count, currently on Azithromycin (Azithromycin) and Augmentin (Amoxicillin-Clavulanate)?

Evaluation and Management of Lymphocytosis in an Elderly Asthmatic Patient

Immediate Clinical Assessment Required

This patient's absolute lymphocytosis (8,662 cells/µL) with relative lymphocyte predominance (61%) and leukocytosis (14.2 × 10⁹/L) requires immediate evaluation to distinguish between viral infection, medication effect, or underlying lymphoproliferative disorder. 1

The laboratory pattern shows:

• Marked absolute lymphocytosis (normal range: 1,000-4,800 cells/µL) 1
• Relative neutropenia (33.7%) with normal absolute neutrophil count (4,785 cells/µL) 1
• Leukocytosis without left shift or bandemia 1

This pattern is atypical for bacterial infection, which typically presents with neutrophilia and lymphopenia, not lymphocytosis 2. The absence of elevated neutrophil percentage and the presence of marked lymphocytosis suggest this is not a typical bacterial pneumonia or acute asthma exacerbation requiring antibiotics 1, 2.

Differential Diagnosis Priority

Most Likely: Viral Infection or Post-Viral State

• Viral respiratory infections characteristically cause lymphocytosis, unlike bacterial infections which cause neutrophilia and lymphopenia 2, 3
• The patient's asthma history makes viral respiratory infection a primary concern, as viral stimuli are a major cause of asthma exacerbations 4
• Absolute lymphocyte counts >5,000 cells/µL warrant investigation for infectious mononucleosis, pertussis, or other viral syndromes 1

Alternative Consideration: Medication Effect

• Azithromycin accumulates massively in lymphocytes (cellular to extracellular ratio of 387:1) and may alter lymphocyte trafficking 5
• However, azithromycin typically does not cause lymphocytosis of this magnitude 6, 5

Must Exclude: Chronic Lymphocytic Leukemia (CLL)

• In elderly patients, persistent absolute lymphocytosis >5,000 cells/µL raises concern for CLL 1
• This requires peripheral blood smear examination and flow cytometry if lymphocytosis persists 1

Immediate Next Steps

1. Reassess Clinical Status and Asthma Control

• Measure peak expiratory flow immediately to assess current asthma control 1, 7
• Evaluate for signs of severe asthma exacerbation: inability to complete sentences in one breath, respiratory rate >25/min, heart rate >110 bpm, oxygen saturation <92% 7, 8
• If PEF <50% predicted or oxygen saturation <92%, immediate hospitalization is required 7, 8

2. Discontinue Antibiotics Immediately

• Antibiotics should only be used if bacterial infection is clearly documented 1, 7, 9
• This patient's laboratory pattern (lymphocytosis, not neutrophilia) does not support bacterial infection 2
• Both Azithromycin and Augmentin should be stopped unless there is documented bacterial pneumonia, purulent sputum with positive culture, or consolidation on chest radiograph 1

3. Obtain Peripheral Blood Smear

• Manual differential is essential to assess lymphocyte morphology and exclude atypical lymphocytes (viral) versus mature small lymphocytes (CLL) 1
• Look specifically for atypical/reactive lymphocytes suggesting viral infection versus monomorphic small mature lymphocytes suggesting CLL 1

4. Optimize Asthma Management

• Initiate or reinitiate oral prednisone 30-60 mg daily for 1-3 weeks if the patient has ongoing asthma symptoms or recent exacerbation 7, 9, 8
• High-dose inhaled corticosteroids should be continued or initiated 7, 8
• Provide albuterol nebulizer or MDI with spacer for rescue therapy every 4 hours as needed 7, 9

Follow-Up Laboratory Testing (Within 1-2 Weeks)

If Lymphocytosis Persists:

• Repeat complete blood count with manual differential 1
• Flow cytometry for lymphocyte immunophenotyping if absolute lymphocytosis remains >5,000 cells/µL 1
• Consider viral serologies (EBV, CMV) if atypical lymphocytes present 1

Additional Testing to Consider:

• Chest radiograph only if clinical signs suggest pneumonia, consolidation, or pneumothorax—not routinely indicated 1
• Sputum culture only if purulent sputum is present 1

Critical Pitfalls to Avoid

1. Do not continue antibiotics without documented bacterial infection 1, 7—this patient's lab pattern suggests viral etiology or non-infectious cause

2. Do not assume leukocytosis equals bacterial infection—the lymphocyte predominance pattern is inconsistent with bacterial infection and more consistent with viral infection 2, 3

3. Do not ignore persistent lymphocytosis in elderly patients—absolute lymphocytosis >5,000 cells/µL persisting beyond 2-4 weeks requires hematologic evaluation for CLL 1

4. Do not use sedatives if respiratory symptoms are present, as they are absolutely contraindicated in asthma 1, 9

5. Do not discharge without ensuring adequate corticosteroid duration—if this represents asthma exacerbation, prednisolone should be continued for 1-3 weeks, not just 5-6 days 7, 9

Monitoring Plan

• Recheck CBC with differential in 1-2 weeks to assess whether lymphocytosis is transient (viral) or persistent (CLL) 1
• Peak flow monitoring at home with written asthma action plan 7, 8
• Primary care follow-up within 1 week and respiratory specialist within 4 weeks if asthma symptoms persist 7
• If lymphocytosis persists >4 weeks with absolute count >5,000 cells/µL, refer to hematology for CLL evaluation 1