History

You have a medical student, Joanna, working with you in clinic today. She sees the patient and presents the case to you as follows:

“This is a 47 year-old woman who is referred to us for evaluation of elevated white cells. She was first noted to have leukocytosis about 2 years ago when her PCP ordered a routine complete blood count. She has no prior history of elevated blood counts. She doesn’t complain of any infections. She also has a history of hypertension and hypothyroidism. She had an appendectomy when she was in her 20s. She has no family history of leukocytosis or other hematological disorders. She smokes 2 packs of cigarettes per day and she drinks 2-3 glasses of wine each week. She is taking lisinopril and L-thyroxine, and she has no known allergies.”

Are you happy with this presentation? Could it be improved upon? What advice would give Joanna?

To answer this question, we need to consider the differential diagnosis of leukocytosis and then work our way backward to important negatives and positives in the history.

Before getting into the nitty gritty, it is helpful to consider some general principles:

The total white count is the sum of the number of different subsets of white cells, which in normal conditions includes:
- Neutrophils
- Lymphocytes
- Monocytes
- Eosinophils
- Basophils
In leukocytosis, it is possible to have different combinations of normal, reduced and elevated counts in different white cell subsets.
Elevation and reduction in each of these subset counts carries a unique differential diagnosis.
Thus, there are many permutations to consider!
The differential diagnosis of leukocytosis is, of course, context-dependent, for example:
- Incidental finding vs. finding in a symptomatic patient
- Inpatient vs. outpatient
- Acute vs. chronic
An important goal in the work-up a patient with leukocytosis is to distinguish between primary (clonal) and reactive causes.

In this case, we do not yet know the white blood cell differential (the breakdown in counts according to the 5 white cell subsets). However, the finding was incidental, the patient is asymptomatic, and the problem has persisted for at least two years. With that in mind, let’s consider the differential diagnosis in broad strokes:

Neutrophilia

Primary (clonal)
Reactive:
- Infection
- Chronic inflammation
- Smoking
- Stress
- Obesity/metabolic syndrome
- Drugs:
  - Corticosteroids
  - Beta-agonists
  - Lithium
  - Epinephrine
- Hypercortisolism
- Postsplenectomy state
- Nonhematologic malignancy (paraneoplastic)

Monocytosis

Primary (clonal)
Reactive:
- Viral or bacterial infection
- Corticosteroids
- Malignancy
- Postsplenectomy state
- Autoimmune disorders (such as inflammatory bowel disease or sarcoidosis)
- Vasculitides

Lymphocytosis

Primary (clonal)
Reactive:
- Viral, bacterial, or parasitic infection
- Vaccinations
- Connective tissue disease
- Smoking

Eosinophilia

Primary (clonal)
Reactive:
- Allergies
- Tissue-invasive parasites
- Drug reactions

Basophilia – rare, often associated with myeloproliferative neoplasms

Now that we have considered the differential diagnosis, let’s reorganize the history so that it covers the important positives and negatives in red (with comments in brackets):

This is a 47 year-old woman with is referred to us for evaluation of elevated white cells (reason for referral). She was first noted to have leukocytosis about 2 years ago (establishes chronicity) when her PCP ordered a routine complete blood count (incidental finding). She has no prior history of elevated blood counts. She doesn’t complain of any infections. She denies any history or symptoms of an inflammatory disorder. She has never had a splenectomy. She smokes 2 packs per day (note we have moved this important positive from social history to the history of presenting problem). She is not overweight and she does not take corticosteroids or lithium. She denies seasonal allergies or other history of atopy. She has not traveled out of the country in the past 2-3 years and she has no abdominal complaints. Her weight is stable, and she denies fever or night sweats. Her other medical problems include hypertension and hypothyroidism. She had an appendectomy when she was in her 20s. She has no family history of leukocytosis or other hematological disorders. As I mentioned, she is a smoker. She drinks 2-3 glasses of wine each week. She is taking lisinopril and L-thyroxine, and she has no known allergies.

Now, the history of presenting problems (leukocytosis) is nicely fleshed out with relevant positive and negative details. We are ready to move on to the physical exam.

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