Case management study Walter Reed Army Medical Center: Dyspnea on exertion, fatigue, and pallor in a 50-year-old active duty soldier

Military Medicine, Jul 2003 by Verma, Pramvir S, Gallagher, Christopher M

Objective: To discuss a comprehensive diagnostic approach to an active duty patient presenting with dyspnea on exertion, fatigue, and pallor. A 50-year-old active duty E-6 white male in Al Udeid, Qatar, presented with progressive dyspnea on exertion, fatigue, and new pallor. This case illustrates the course of events from Al Udeid to the Walter Reed Army Medical Center, where the final diagnosis was made. Along the way, questions with discussions explore the various diagnostic and management aspects of his case and highlight military relevant issues that include efficient diagnostic algorithms in the field and transfusion of scarce blood products.

Introduction

A 50-year-old active duty E-6 white male was deployed in February 2002 to Al Udeid, Qatar. A week into his deployment, he presented to the infirmary with a fever of 104.0[degrees]F, rigors, dyspnea on exertion, and a cough productive of green sputum for 2 days. He denied any other symptoms and a chest X-ray showed a left lower lobe infiltrate. The patient was treated with a 10-day course of levofloxacin, but noted residual dyspnea on exertion and fatigue. In April, he again presented to the infirmary with continuing dyspnea on exertion, fatigue, and newly observed pallor. He was afebrile and denied cough, orthopnea, paroxysmal nocturnal dyspnea, swelling, wheezing, or bleeding. A review of systems was otherwise negative.

1. In addition to a complete history and physical, which of the following should be pursued NEXT to expeditiously determine his diagnosis?

a. Complete blood count

b. Chest X-ray

c. Transthoracic echocardiogram

d. Serum measurement of thyroid-stimulating hormone

e. Urinalysis

Formulating an efficient diagnostic approach to common medical complaints is essential to the military physician, particularly when operating in deployments where resources are limited. A complete blood count to evaluate for anemia would be the best initial test because anemia would explain each of the patient's symptoms- dyspnea, fatigue, and pallor. Although a chest X-ray can show causes for dyspnea and fatigue, such as pneumonic processes, pleural and pericardial effusions, malignant lesions or adenopathy, and pulmonary vascular congestion, it would be less efficient than the complete blood count in explaining the patient's pallor. Of note, the presence of a radiographic infiltrate in this patient may not be helpful, since an infiltrate from a previous pneumonia can take 4 to 12 weeks to resolve depending on the patient's age and cardiopulmonary status.

The absence of orthopnea, paroxysmal nocturnal dyspnea, or lower extremity swelling argues against a diagnosis of a cardiomyopathy; thus, a transthoracic echocardiogram would likely not be helpful. Similarly, although hypothyroidism can cause pulmonary symptoms, fatigue, and pallor, his age, onset of symptoms, and lack of other manifestations make a serum thyroid-stimulating hormone a low yield test. Finally, a urinalysis may indicate proteinuria and thus potentially lead to a diagnosis of nephrotic syndrome, which can also present with pulmonary symptoms and fatigue. However, the absence of generalized swelling makes this diagnosis unlikely.

A complete blood count was ordered which showed a white blood cell count of 1.2/mm^sup 3^ (4.8-10.8/mm^sup 3^), with no manual differential available, hemoglobin of 3.0 g/dL (14.0-18.0 g/dL), and platelets of 16/mm^sup 3^ (130-400/mm^sup 3^).

2. The patient's complete blood count can be explained by all of the following EXCEPT

a. Parvovirus B19 infection

b. Paroxysmal nocturnal hemoglobinuria

c. Hypothyroidism

d. B12 deficiency

e. Lymphoma

Simultaneously reduced values for the white blood cell, red blood cell, and platelet indices indicate that the patient has pancytopenia. The differential for pancytopenia is quite extensive and includes infection by parvovirus B19. This virus is more commonly associated with a pure red blood cell aplasia, but can also damage the pluripotent stem cells of the bone marrow, resulting in pancytopenia. Other viruses that can cause pancytopenia include the non-A,B,C hepatitis viruses, human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV).1 Paroxysmal nocturnal hemoglobinuria is a syndrome in which acquired genetic defects in stem cell membrane proteins lead to bone marrow failure and a resultant pancytopenia. Also, patients with paroxysmal nocturnal hemoglobinuria are commonly hypercoaguable, have a hemolytic anemia, and often develop myelodysplastic disorders or acute leukemia.2 Hypothyroidism is not associated with pancytopenia. The hematological effects of hypothyroidism are limited to a decrease in red blood cell mass with a resultant normocytic anemia. Vitamin B12 deficiency, more commonly known for causing a macrocytic anemia, also causes pancytopenia. This occurs via concomitant methionine deficiency and deficient conversion of deoxyuridate to thymidylate-hindering DNA synthesis, thus leading to slowed nuclear maturation.3 Finally, lymphoma can cause pancytopenia through direct infiltration of the bone marrow and subsequent replacement of stem cells.