Role and Interpretation of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in HIV-Infected Patients With Fever of Unknown Origin

A Prospective Study

C Martin; C Castaigne; M Tondeur; P Flamen; S De Wit

Disclosures

HIV Medicine. 2013;14(8):455-462. 

In This Article

Abstract and Introduction

Abstract

Objectives The aim of the study was to evaluate prospectively the usefulness of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in investigation of fever of unknown origin (FUO) in HIV-positive patients and to determine whether HIV viraemia impacts on FDG-PET/CT performance.

Methods The FDG-PET/CT results of 20 HIV-infected patients with FUO were analysed and compared with the FDG-PET/CT results of 10 HIV-infected viraemic patients without FUO. The performance of FDG-PET/CT for identifying the aetiology of FUO was assessed. Final diagnosis for FUO was based on histopathology, microbiological assays, or clinical and imaging follow-up.

Results FDG-PET/CT contributed to the diagnosis or exclusion of a focal aetiology of the febrile state in 80% of patients with FUO. The presence of increased FDG uptake in the central lymph node has 100% specificity for focal aetiology of fever, even in viraemic patients. The absence of hypermetabolic central lymph nodes in FUO patients has 100% negative predictive value for focal disease. Lymph node biopsy in central hypermetabolic areas allowed, in 100% of cases, identification of underlying disease in patients with FUO. Biopsy of peripheral lymph nodes should be performed in lymph nodes with maximum standardized uptake value (SUVmax) ≥ 6–8 (sensitivity 62.5%; specificity 75%) and avoided in lymph nodes with SUVmax = 0–4 (specificity 0%). High HIV viraemia does not prevent correct interpretation of FDG-PET/CT.

Conclusions As in HIV-negative patients, we confirm the usefulness of FDG-PET/CT in investigation of FUO in HIV-positive patients even if they are viraemic.

Introduction

Fever of unknown origin (FUO) is a challenging clinical entity frequently encountered in HIV-positive patients. As in nonimmunosuppressed patients, the aetiology of FUO can be infectious, inflammatory, allergic or malignant. In HIV-infected patients, infectious aetiologies account for the majority of FUO[1–3] but may have atypical clinical presentation, which may delay the diagnosis. This has been well described for tuberculosis, one of the most frequent causes of FUO in HIV-infected patients, for whom conventional radiology is less sensitive and who present with extrapulmonary involvement in 60 to 70% of cases.[4]

Inflammatory cells such as macrophages, lymphocytes, neutrophils and even fibroblasts have been shown to be avid for fluorodeoxyglucose (FDG) following stimulation by multiple cytokines, which increases the number of cell surface glucose transporters and hence increases the level of glycolysis. This explains the recognized role of FDG-positron emission tomography/computed tomography (PET/CT) in non-oncological indications for several years.[5,13,14,15]

The advantages of the technique are a whole-body evaluation with available results within 4 hours, potentially allowing accurate localization of the etiology of the problem.

FDG-PET(/CT) has been well validated in the work-up of FUO in HIV-negative patients,[6–10] but only two small studies have been performed in HIV-positive patients with FUO,[11,12] one of which was conducted in the pre-highly active antiretroviral therapy (HAART) era.[12]

Several studies on FDG-PET/CT in HIV-infected patients have shown increased FDG uptake in lymph nodes that could reflect sites of HIV replication.[16–22] Some of these studies suggest that asymptomatic HIV-infected patients with fully suppressed HIV viral loads (VLs) have no or little FDG uptake in lymph nodes, whereas patients with detectable VLs show FDG uptake in several lymph node groups, predominantly in cervical and axillary areas, followed by the inguinal area, according to the stage of the disease.[18–20] A correlation between FDG-PET signal and HIV viraemia was found in two studies[17,19] but another study did not find such a correlation.[21] Metabolism of reactive lymph nodes can thus be variable[18,21] and, when increased, can decrease the specificity of FDG-PET/CT in viraemic HIV-infected patients.[22,23] This must be taken into account when interpreting FDG-PET/CT imaging in HIV-infected patients.[12,16]

To assess whether HIV VL could be a confounding factor in interpreting FDG-PET/CT of patients with FUO, we compared HIV-infected patients who had FUO with viraemic HIV-infected patients who did not have FUO.

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