Lymphopenia of undetermined etiology

Madeleine Verhovsek, MD, is an associate professor in the Department of Pathology and Molecular Medicine at McMaster University.

What should be the diagnostic approach to lymphopenia of undetermined etiology?

Lymphopenia is a very tricky one because it can be present for so many reasons. Probably the most common ones that we see are someone who has had a virus and the lymphocyte count goes down after the virus, or someone who just has other medical issues—they’re malnourished, someone who is frail and elderly. Those are often the causes of lymphopenia.

It requires some clinical judgment. We need to decide: do we feel confident that we have an explanation for the lymphopenia? If we feel confident that we have an explanation and also if the patient is looking very well, is not having any infections—those are all good reasons that we don’t need to necessarily jump into very extensive investigations.

On the flip side, if the patient is medically unwell, if they’re sick, if they have an illness, if they’re demonstrating any features, for example, of chronic viral hepatitis, HIV, or other undiagnosed either infectious or noninfectious illness, also if the patient has had recurrent or severe infections in the past—that may be a marker of them having an inherited immunodeficiency. Those are all reasons why we would want to take it very seriously, make sure that we get to the bottom of the case, so that we can maybe take action to correct whatever the underlying problem is.