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[Dr. Shapiro] This is Dr. Samantha Shapiro, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. And now, onto the episode.
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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts, I'm Dr. Cathy Handy.
[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to episode 98, a 68-year-old with fatigue, intermittent fevers, and night sweats. Okay, Cathy, so today's patient is a 68-year-old woman who comes to the clinic with fatigue, intermittent fevers, and night sweats for the past two weeks. She denies any recent travel or sick contacts. Her physical examination reveals pale conjunctiva but is otherwise totally normal. Her vital signs are notable only for a temperature of 38.0 degrees centigrade. She has some lab tests, and her metabolic panel is normal, but her complete blood count reveals a white blood cell count of 800 per microliter, a hemoglobin of 8 grams per deciliter, and a platelet count of 98,000 per microliter.
[Dr. Handy] All right, let's stop right there for a minute. So the patient's likely to get admitted to the hospital with that low white blood cell count and fever. Now, we define severe neutropenia as an absolute neutrophil count of less than 500, and she's likely around there. While there are some scores that can be used to help determine inpatient or outpatient management, if this is all a new diagnosis, then I would think that inpatient workup is indicated. Does she have any past medical history that would be relevant or is she receiving any medications?
[Dr. Wiener] Yeah, so she's a retired attorney who's maintained excellent health. She does spend time watching her grandchildren, who range from 3 to 13 years old. Her only medications are atorvastatin and occasional Prilosec when her grandchildren are a little bit rowdy.
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[Dr. Wiener] What medications were you worried about?
[Dr. Handy] Well, besides the obvious chemotherapeutic agents, some antibiotics can cause pancytopenia, but those don't sound relevant in this case. What does the question ask?
[Dr. Wiener] Okay, so this is an exclusion case. The question asks, which of the following is least likely to cause her current symptoms? And the options are, A. acquired aplastic anemia; B. copper deficiency; C. myelodysplastic syndrome; D. myelofibrosis; or E. parvovirus infection.
[Dr. Handy] Well, to sum up her presentation, she has pancytopenia because of the decrease in white blood cell count, hemoglobin, and platelets. You didn't tell me the differential of the white blood cell count, which can sometimes be helpful. And she's also reporting B type symptoms with fatigue, night sweats, and intermittent fevers. Clearly, myelodysplastic syndrome and closely related myelofibrosis can cause this presentation. They're both classified as myeloproliferative malignancies and typically present with symptoms related to pancytopenia, so that can sometimes include bruising, infection, or anemia and that's what we see in this patient.
[Dr. Wiener] Okay, so option C. is true, and option D. is true, what about option A. aplastic anemia?
[Dr. Handy] Despite its name, aplastic anemia will typically present with a pancytopenia so that the white blood cell count and platelet counts are also reduced, again, as in this case. Aplastic anemia may be caused by drugs or exposures to radiation, but patients like this most likely have the form that is mediated by T cell autoimmunity.
[Dr. Wiener] Okay, so that leaves us with either copper deficiency, option B. or option E. parvovirus infection. Which one of those is not the cause in this case?
[Dr. Handy] Well, copper deficiency can mimic myeloproliferative disorders, particularly with anemia and leukopenia, but most patients have other nutritional deficiencies or a history of gastric surgery with malabsorption. So we have to keep that in the differential for now.
[Dr. Wiener] So I guess that leaves E. parvovirus infection as the answer. That doesn't cause the pancytopenia?
[Dr. Handy] All right, well, the history of watching the grandchildren clearly was trying to lead us towards the parvovirus B19 infection which causes fifth disease. We toss this diagnosis out a lot, but it's important to remember that parvovirus B19 infection is associated with isolated temporary red blood cell failure leading to anemia, not pancytopenia. Most patients will have a temporary reduction in red blood cell production, but not enough to be symptomatic. However, certain patients can be severely affected, so patients with sickle cell disease, for example, who have high red blood cell turnover may become symptomatic.
[Dr. Wiener] Okay, so we now know the answer is E. parvovirus that's not a cause of this lady's pancytopenia, but before we leave, give us a few words on the evaluation and differential diagnosis of a patient with pancytopenia.
[Dr. Handy] Well, we've alluded to some of it, a good medication and exposure history is essential. As far as blood work is concerned, it's vital to look at the peripheral smear and check for nutritional deficiencies, but some patients may also need a bone marrow aspirate and biopsy to establish a definitive diagnosis.
[Dr. Wiener] And the differential?
[Dr. Handy] The differential is based on the appearance of the bone marrow. If the marrow is hypocellular, then you think of aplastic anemia, nutritional deficiencies, which can also include chronic alcohol use, or some of the myelodysplastic syndromes. If the marrow is cellular, then you worry about the primary bone marrow diseases, including malignancies, or infections, which can involve the bone marrow, such as tuberculosis, HIV, or sepsis.
[Dr. Wiener] Great, so the teaching points in this case are that pancytopenia may present with symptoms relating to the deficiency in any one of the three bone marrow lines. The differential diagnosis may include malignant, nutritional, or infectious causes, and the diagnosis may rely on examination of the bone marrow. Parvovirus B19 infection, which causes fifth disease in children, does not cause pancytopenia.
[Dr. Handy] And you can read more about this in Harrison's chapter on bone marrow failure syndromes.
[Dr. Shapiro] Thanks for listening to Harrison's Podclass. You can listen to this episode and more on AccessMedicine.com, which includes the complete Harrison's Principles of Internal Medicine text, Harrison's review questions, which compliment and expand upon the questions in this episode, and much more. AccessMedicine.com may already be available to you via your academic institution. Check it out.
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