Radiological imaging in the context of HIV infection: size of the lesion is not everything.
Article Type: Editorial
Subject: HIV infection (Diagnosis)
HIV infection (Care and treatment)
Radiography (Usage)
Authors: Descamps, Marjanne J.L.
Hatzimichael, Eleftheria
Bhuva, Neel
Stebbing, Justin
Pub Date: 09/01/2008
Publication: Name: Journal of HIV Therapy Publisher: Mediscript Ltd. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2008 Mediscript Ltd. ISSN: 1462-0308
Issue: Date: Sept, 2008 Source Volume: 13 Source Issue: 3
Geographic: Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom
Accession Number: 200343551
Full Text: This edition of the Journal of HIV Therapy is devoted to the imaging of different pathologies in the context of HIV infection. We are fortunate to have some truly superb papers with accompanying striking images. These teach us that the observation of subtle defects can immediately lead to diagnoses with enormous implications for the patient; such conditions are seldom observed outside HIV. In particular, Occam's razor, the principle named after William of Occam, a 14th-century philosopher, does not apply in this setting. This generalisation states that if there are a number of explanations for observed phenomena, the simplest explanation is preferred--called also scientific parsimony. Rare manifestations of common diseases and common presentations of rare conditions may be seen together; only HIV and its subsequent immunosuppression link these phenomena [1]. Fortunately, with the advent of HAART in established market economies, the spectrum has changed with a notable shift from infection to cancer [2] and 'standard' diseases that non-HIV-infected people are routinely affected by, including non-AIDS-defining malignancies.

The lessons we learn here have been useful in the most unusual of circumstances. Natalizumab, a humanised monoclonal antibody against [[alpha].sub.4] integrins, used to treat multiple sclerosis was found to cause progressive multifocal leukoencephalopathy (PML) in 1 in 1000 patients. Three years ago, shortly after its launch, it was withdrawn from the market as the occurrence of PML in this setting was totally unexpected [3]. It appears that natalizumab, by preventing the normal trafficking of lymphocytes, leads to unbridled JC virus replication contributing to the development of PML. Arriving at this diagnosis is challenging, and mistaking PML for a primary brain tumour, a stroke or even progression of multiple sclerosis may occur. Its not infrequent occurrence in the setting of HIV has taught us that the imaging findings of a multifocal process that is limited to the white matter and that exhibits neither mass effect nor enhancement with contrast material should always raise the suspicion of PML. In the absence of a contraindication to lumbar puncture, the demonstration of a positive result on polymerase chain reaction for JC virus in the cerebrospinal fluid establishes the diagnosis when coupled with the appropriate clinical and radiological features. These are old lessons for experienced HIV clinicians who have often observed immune reconstitution [4,5], but they have helped enormously in the understanding of a rare side-effect with a new drug in a totally unrelated disease.

Jager and colleagues discuss beautifully the major CNS pathologies that are likely to be encountered, and the optimal methods used to visualise these. Winston and collaborators have described the increasing role of magnetic resonance imaging and spectroscopy of the brain in two ways: structural and functional. Proton magnetic resonance spectroscopy allows the measurement of CNS metabolites in different areas in the brain, based on the principles that protons behave differently in changing environments. Functional MRI studies suggest that HIV-positive subjects including those not on HAART have a reduction in attention networking such that frontal lobes utilise more oxygen to perform certain tasks. The long-term effects deserve attention here, as well as increasing our understanding of the role of different antiretroviral agents with contrasting cerebrospinal fluid penetration. Perhaps 'older' drugs such as nevirapine deserve closer attention due to physiologically relevant levels being present in the cerebrospinal fluid [6].

Monkemuller et al. have written a fascinating review of gastrointestinal pathology. The frequent occurrence of multiple simultaneous disease processes such as CMV, Mycobacterium avium complex and Candida together makes a definitive diagnosis essential; the diagnosis of idiopathic lesions is purely by exclusion.

Robert Yarchoan's team discuss broad imaging techniques for Kaposi's sarcoma. Here, precise staging and the documentation of every tumour site is less important as the disease is multifocal and driven by a virus. A major issue, however, in clinical trials is the documentation of lesions and the extent that disease changes with therapy, even though we have previously shown that the stage of disease does not appear to influence prognosis [7]. The merits of visible light photography, ultrasound, infrared thermal imaging, standard plain radiographs, CT and MRI are clearly described and are now established. Multispectral imaging, use of the radioactive nucleoside analogue FIAU, which is concentrated in cells harbouring KSHV, and imaging probes targeting matrix metalloproteinases have the potential to become valuable research tools with broad applicability.

Finally, Bower et al. talk about imaging of another KSHV-driven neoplasm: multicentric Castleman's disease (MCD). Preliminary data suggest that FDG PET-CT assists in the monitoring of disease activity in MCD along with familiar clinical and laboratory tools including plasma KSHV DNA viral load measurement. A difficulty here is that HIV-MCD remains rare, thereby prohibiting larger studies.

The challenges for diagnosis and management of sick people with HIV remains, and imaging is a central part of our armamentarium here. Extending this to resource-poor settings will be a priority in the coming years.

REFERENCES

[1.] Stebbing J, Gazzard B, Douek DC. Where does HIV live? N Engl J Med, 2004, 350, 1872-1880.

[2.] Stebbing J, Bower M. What can oncologists learn from HIV? Lancet Oncol, 2003, 4, 438-445.

[3.] Berger JR, Koralnik IJ. Progressive multifocal leukoencephalopathy and natalizumab: unforeseen consequences. N Engl J Med, 2005, 353, 414-416.

[4.] Wiley CA, Grafe M, Kennedy C, Nelson JA. Human immunodeficiency virus (HIV) and JC virus in acquired immune deficiency syndrome (AIDS) patients with progressive multifocal leukoencephalopathy. Acta Neuropathol, 1988, 76, 338-346.

[5.] Rhodes RH, Ward JM, Walker DL, Ross AA. Progressive multifocal leukoencephalopathy and retroviral encephalitis in acquired immunodeficiency syndrome. Arch Pathol Lab Med, 1988, 112, 1207-1213.

[6.] Bower M, Powles T, Nelson M et al. Highly active antiretroviral therapy and human immunodeficiency virus-associated primary cerebral lymphoma. J Natl Cancer Inst, 2006, 98, 1088-1091.

[7.] Stebbing J, Sanitt A, Nelson M et al. A prognostic index for AIDS-associated Kaposi's sarcoma in the era of highly active antiretroviral therapy. Lancet, 2006, 367, 1495-1502.

Correspondence to: Justin Stebbing, Imperial College Healthcare NHS Trust, London, UK. Email: j.stebbing@imperial.ac.uk
Gale Copyright: Copyright 2008 Gale, Cengage Learning. All rights reserved.