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An incidental finding of occult HIV infection.

To the Editor: A 45-year-old woman presented with a 6-month history of progressively worsening leg swelling. The patient was otherwise previously healthy. On physical examination, jugular venous pressure was elevated to the angle of the jaw. There were fine crackles at her lung bases. Precordial examination demonstrated a parasternal parasternal /para·ster·nal/ (-ster´n'l) situated beside the sternum.


beside the sternum.
 heave and a loud second heart sound. A Grade 2/6 holosystolic murmur was detected along the left sternal sternal /ster·nal/ (ster´n'l) of or relating to the sternum.

Of, relating to, or occurring near the sternum.


pertaining to the sternum.
 border. There was bilateral pitting edema up to her proximal thighs. An echocardiogram ech·o·car·di·o·gram
A visual record produced by echocardiography.

A non-invasive ultrasound test that shows an image of the inside of the heart.
 revealed functional tricuspid tricuspid /tri·cus·pid/ (tri-kus´pid) having three points or cusps, as a valve of the heart.

An organ or a part, especially a tooth, having three cusps.

 valvular regurgitation secondary to severe right ventricular dilation and hypokinesis. Right ventricular pressure was elevated at approximately 75 mm Hg, consistent with pulmonary hypertension (PH). Subsequent tests were ordered to elucidate the etiology of her PH, including a connective tissue workup, pulmonary function tests, coronary angiogram an·gi·o·gram
An angiographic x-ray of blood vessels used in diagnosing pathological conditions of the cardiovascular system.//An x-ray of one or more blood vessels produced by angiography and used in diagnosing pathology in the cardiovascular
, and CT scans for pulmonary embolism, all of which were negative. Surprisingly, a HIV test was performed and found to be positive on confirmatory Western blot. CD4 lymphocyte count was approximately 500 [mm.sup.3]. She denied exposure to HIV risk factors. The patient was subsequently placed on a diuretic, [beta]-blocker, and an ACE inhibitor with good response. She was also referred to the outpatient HIV clinic for close follow up and consideration for highly active antiretroviral therapy (HAART).

PH is a rare systemic manifestation of HIV infection, first reported by Kim et al in 1987 in an end-stage AIDS patient who presented with dyspnea and renal insufficiency. (1) Subsequent series have clearly documented an association between HIV and PH, which can lead to profound right-sided heart failure right-sided heart failure Right heart failure Cardiology A disorder in which the right side of the heart loses its ability to pump blood efficiently, often a complication of other disorders Etiology Left-sided heart failure, COPD, emphysema, congenital heart  and a universally poor prognosis. (2,3) The current case is unique because to our knowledge it is the first to describe bilateral leg swelling as the presenting symptom of HIV and associated PH. With improved survival and a more prolonged natural history of disease owing to the widespread use of HAART, it is anticipated that more clinicians will be presented with the important task of managing the late and often systemic manifestations of HIV, such as PH.

PH occurs when mean pulmonary arterial pressure exceeds 25 mm Hg at rest or 30 mm Hg with exercise. Unlike the current case, most patients with PH initially present with fatigue, lethargy, and decreased exercise tolerance. Leg edema can occur but usually exclusively during the late stages of disease when there has been definite progression to right ventricular failure right ventricular failure
Congestive heart failure manifested by distention of the neck veins, enlargement of the liver, and dependent edema.

The gold standard for the diagnosis of PH is right heart catheterization right heart catheterization Pulmonary artery catheterization Cardiology A technique for direct measurement of cardiac function, consisting of the introduction of a catheter into the right atrium, right ventricle, pulmonary artery Data Hemodynamic measurements, , but it is often possible to reliably establish the diagnosis with less invasive methods, such as the use of echocardiography Echocardiography Definition

Echocardiography is a diagnostic test that uses ultrasound waves to create an image of the heart muscle. Ultrasound waves that rebound or echo off the heart can show the size, shape, and movement of the heart's valves and
 to indirectly estimate pulmonary artery pressure. (4) Additional investigations should be performed to rule out more common secondary causes of PH, including collagen vascular conditions, chronic pulmonary emboli, and restrictive lung diseases. The specific diagnosis of HIV-associated PH is often more challenging as the clinical and histopathologic features of this entity do not differ drastically from those of primary or idiopathic PH. Therefore, as in this case, a high index of suspicion index of suspicion Medtalk A phrase broadly used to indicate how seriously a particular disease is being entertained as a diagnosis; as an example, there is a high IOS that rapid and unexplained weight loss in an elderly Pt is due to pancreas CA, and a low IOS that  is warranted and the diagnosis is frequently confirmed once other causes have been carefully excluded. In this patient, HIV seropositivity was the only laboratory abnormality found in conjunction with pulmonary hypertension.

The underlying etiology and pathophysiology of HIV-associated PH remains unclear. Genetic susceptibility, environmental factors, and viral characteristics are believed to play important roles. The fact that this patient developed HIV-associated PH despite a CD4 lymphocyte count of approximately 500 [mm.sup.3] suggests that the degree of immunodeficiency is a poor predictor of whether an individual will develop PH.

Typically, a combination of supplemental oxygen, bosentan, ACE inhibitors, and calcium channel blockers Calcium Channel Blockers Definition

Calcium channel blockers are medicines that slow the movement of calcium into the cells of the heart and blood vessels.
 are used to provide patients with some symptomatic relief. Currently, the role of HAART in the treatment of HIV-associated PH remains uncertain since most studies have been retrospective in nature or have involved only small numbers of patients. (5) More importantly, it is unclear whether HAART influences the progression or prognosis of HIV-associated PH. The widespread use of HAART has altered the natural history of HIV such that more patients are living long enough to display some of the late and systemic manifestations of the infection, such as PH. Although the etiology of PH is quite broad, this case highlights the importance of considering causes like HIV in the differential diagnosis. The presence of bilateral leg swelling in a HIV patient should also raise the clinical suspicion for possible PH and prompt appropriate clinical evaluation.

Winson Y. Cheung, MD

Department of Internal Medicine

University of Manitoba

Winnipeg, Manitoba, Canada


1. Kim KK, Factor SM. Membranoproliferative glomerulonephritis and plexogenic pulmonary arteriopathy plexogenic pulmonary arteriopathy Pulmonary disease A vasculopathy seen in pulmonary HTN, characterized by medial hypertrophy of muscular pulmonary arteries, fibrinoid necrosis Etiology Anorexiants–eg, fenfluramine; possibly phentermine. See Fen-phen.  in a homosexual man with acquired immunodeficiency syndrome acquired immunodeficiency syndrome, see AIDS. . Hum Pathol 1987;18:1293-1296.

2. Mehta NJ, Khan IA, Mehta RN, et al. HIV-related pulmonary hypertension: analytic review of 131 cases. Chest 2000;118:1133-1141.

3. Petitpretz P, Brenot F, Azarian R, et al. Pulmonary hypertension in patients with human immunodeficiency virus human immunodeficiency virus

Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans.
 infection. Comparison with primary pulmonary hypertension. Circulation 1994;89:2722-2727.

4. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines clinical practice guidelines Clinical policies, practice guidelines, practice parameters, practice policies Medtalk Systematically developed statements to assist practitioner and Pt decisions about appropriate health care for specific clinical circumstances. See Psychology. . Chest 2004;126(1 suppl):14S-34S.

5. Zuber JP, Calmy A, Evison JM, et al. Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy. Clin Infect Dis 2004;38:1178-1185.
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Author:Cheung, Winson Y.
Publication:Southern Medical Journal
Article Type:Letter to the editor
Date:Nov 1, 2006
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