Extensive brain masses and cavitary lung lesions associated with toxoplasmosis and acquired immunodeficiency syndrome

Abstract

Toxoplasmosis is an important cause of enhancing brain lesions in patients with acquired immunodeficiency syndrome (AIDS), and it is typically associated with low CD4-lymphocyte counts. Extensive toxoplasma encephalitis when the CD4-lymphocyte count is above 100 cells/µl is unusual. Cavitary lung lesions are also not typically associated with toxoplasmosis. Here, we present a case of toxoplasmosis associated with extensive brain masses and cavitary lung lesions, both of which improved with directed toxoplasmosis therapy, in an AIDS patient with a CD4 cell count of 120 cells/µl.

Keywords

Acquired immunodeficiency syndrome North America

Introduction

Toxoplasmosis is a common cause of enhancing brain lesions in the severely immunocompromised, such as patients with acquired immunodeficiency syndrome (AIDS).¹ Cavitary lung lesions, however, are not common manifestations of toxoplasmosis and should often raise the suspicion of a secondary diagnosis.² We present a case of extensive brain masses coexisting with cavitary lung lesions in a newly diagnosed human immunodeficiency virus (HIV) patient with a CD4 cell count above 100 cells/µl.

Case presentation

History: A 55-year-old man with a recently diagnosed HIV infection presented with headaches, progressive confusion, nonproductive cough, and an unintentional 20 lb weight loss of two months’ duration. He had fever, chills, night sweats, and mild weakness of his right leg. There was no dyspnea, hemoptysis, photophobia, blurred vision, or gastrointestinal symptoms. He smoked one pack of cigarettes per day but had no history of intravenous drug use. He had no pets, specifically no cats and no history of reported feline exposure. He hadn't recently travelled or had any known tuberculosis contacts.

Physical examination: Vital signs were within normal limits. He was cachectic and confused. Coordination was abnormal and gait was unsteady. Heart, lung, and abdominal examinations were unremarkable. Muscle strength, tone, reflexes, and cranial nerve examinations were also within normal limits.

Studies: Laboratory investigations showed a white cell count of 3150 cells/µl, hemoglobin 11 g/dl, and platelets 137,000 cells/µl. Serum creatinine was 0.68 mg/dl and hepatic aminotransferases were within normal limits. HIV-1 RNA viral load was 37,487 copies/ml and CD4 cell count was 120 cells/µl.

Brain magnetic resonance imaging (MRI) showed several ring enhancing, mostly solid lesions with vasogenic edema and 3 mm midline shift. The lesions were described as diffuse with the largest involving the frontal lobes but also involved the thalamus, brain stem, cerebellum, and even meninges (Figures 1 and 2). As part of his admission workup a chest radiograph was obtained, which revealed a right upper lobe infiltrate. Subsequently, chest computed tomography (CT) scan showed a 2.2 cm × 1.7 cm thin-walled cavitary lesion in the right upper lobe with tree in bud abnormalities, and a 1.2 cm × 0.9 cm thick-walled cavitary lesion in the left upper lobe (Figure 3).

Figure 1.

Brain MRI with and without contrast showing multiple ring enhancing lesions in the thalamus, pons, and a few scattered lesions in the cerebrum. MRI: magnetic resonance imaging.

Figure 2.

Brain MRI with and without contrast showing a large lesion in the frontal lobe as well as meningeal based and cerebellar lesions. MRI: magnetic resonance imaging.

Figure 3.

Chest CT scan with intravenous contrast showing 2.2 cm thin-walled cavitary lesion in right upper lobe (red arrow) and a smaller 1.2 cm thick-walled cavitary lesion in left upper lobe (blue arrow). CT: computed tomography.

Figure 4.

Touch preparation of brain tissue (Wright–Giemsa stain) depicting toxoplasma cyst with multiple bradyzoites/tachyzoites (arrows).

Figure 5.

CT chest with IV contrast after eight weeks of toxoplasmosis treatment showing improvement in size of one of the lung cavities. CT: computed tomography.

Figure 6.

CT brain without contrast four months after onset of toxoplasmosis therapy showing encephalomalacia in the right frontal region with complete resolution of toxoplasmic lesions. CT: computed tomography.

Figure 7.

CT brain without contrast four months posttoxoplasmosis therapy showing resolution of previous brain lesions and postsurgical changes. CT: computed tomography.

Clinical course prior to diagnosis

Due to concerns of increased intracranial pressure, lumbar puncture was not done at the time of initial evaluation. The patient’s mental status, however, deteriorated over the next few days and steroids were started.

A brain biopsy was subsequently done and samples were sent for histopathology, bacterial cultures, fungal stains, and fungal and mycobacterial cultures. Touch preparation slides of the brain tissue were obtained and stained by the Wright–Giemsa stain, which showed cystic-like structures with numerous round solid contents (Figure 4). Immunohistochemical staining of the specimen was positive for toxoplasmosis.

Diagnostic procedures and results

After a few days on steroids, cerebrospinal fluid (CSF) was obtained and analysis showed pleocytosis and elevated protein, but was negative for bacterial and fungal cultures. CSF Toxoplasma gondii real-time polymerase chain reaction (PCR) (Applied Biosystems 7500 real-time PCR) analysis was positive with a quantitative value of 236 DNA copies/ml. Toxoplasma IgG in blood (chemiluminescent immunoassay) was also reactive. Gomori methenamine silver stain of brain tissue specimen was negative for any fungal elements. Similarly, bronchoalveolar lavage and biopsy of right upper lobe cavitary lesion yielded no significant finding on microbiologic and histopathologic analysis.

Treatment/follow-up

The patient was treated with sulfadiazine 1 g orally every 6 h, pyrimethamine 50 mg orally daily after a loading dose of 200 mg orally, and leucovorin 25 mg orally daily for six weeks. HIV was treated with emtricitabine/tenofovir disoproxil (Truvada) 200/300, one tablet orally daily and dolutegravir 50 mg orally daily, commenced two weeks after starting toxoplasmosis treatment. The patient had an excellent recovery. At his eight-week follow-up, repeat CT of the lungs with contrast showed definitive interval improvement in the size of one of his lung cavities (1.6 cm × 1.0 cm) (Figure 5). Four months following onset of toxoplasmosis treatment, CT of the brain without contrast showed encephalomalacia with complete resolution of his previously noted brain lesions (Figures 6 and 7).

Discussion

Toxoplasmosis is the most common central nervous system (CNS) infection in patients with HIV/AIDS who are not receiving appropriate prophylaxis, especially when there are concomitant focal neurological signs. The commonest manifestation of toxoplasmosis is in the CNS where it usually presents as one or more mass lesions. The disease is usually seen when the CD4 cell count falls below 100 cells/µl (without prophylaxis), but can occur at higher CD4 cell counts, as in our patient.³ Typically, 90% of patients have CD4 cell counts less than 200 cells/µl, and 75% have CD4 cell counts less than 100 cells/µl at the time of clinical presentation. Per United States guidelines, prophylaxis for toxoplasmosis in the setting of HIV is not recommended until the CD4 cell count is below 100 cells/µl, in contrast to the European guidelines where prophylaxis is recommended when the CD4 cell count falls below 200 cells/µl. Association with cats and other felines has been well described but several patients like our referenced case cannot remember any definite feline association or ever owned a cat.

The presumptive diagnosis of toxoplasmosis in HIV/AIDS is clinical (focal neurological signs), serological (reactive ELISA for toxoplasma antibody IgG), and radiological (one or more ring enhancing brain lesions on contrasted MRI [preferred] or CT scans). Positive PCR for T. gondii in CSF is approximately 100% specific for cerebral toxoplasmosis but sensitivity is poor.⁴ Treatment is usually started on the basis of presumptive diagnosis.

In less straightforward cases, and when there is clinical suspicion of a possible alternate or secondary disease process, brain biopsy may help to clarify diagnosis.⁵ In positive cases, findings may include cysts containing bradyzoites (dormant form) which may coexist with numerous active tachyzoites as demonstrated by our case (Figure 4).

Cavitary lung lesions are not typical with toxoplasmosis and search for other etiologies should always be entertained.² Pulmonary involvement by toxoplasmosis is often nonspecific but more commonly described findings include interstitial pneumonitis, necrotizing pneumonitis, consolidations, pleural effusion, empyema, or combination of some or all of these.^6–8 In our patient however, extensive workup of the lung lesions yielded no alternative diagnosis and follow-up chest imaging showed improvement with toxoplasmosis treatment implying a possibility that these cavities may have been associated with toxoplasmosis.

Empirical treatment for toxoplasmosis is reasonable when the clinical presentation and preliminary work up is suggestive, pending definitive diagnosis.⁹ The atypical presentation of our patient (lung cavities, multiple diffuse lesions, relatively high CD4 cell count), however, prompted obtaining a brain biopsy, specifically looking for a secondary or possible alternate diagnosis.

The use of steroids in the management of toxoplasmosis could be beneficial especially in patients with large lesions producing significant mass effect and impending cerebral herniation.¹⁰ However, caution should be exercised when the diagnosis is not established, as steroids use by itself may produce clinical and radiologic improvement of undiagnosed and untreated toxoplasma lesions, thereby providing false assurance. Moreover, in at least one study, there was no difference in treatment response rate between those who received steroids and those who did not.¹¹ In patients with suspected impending herniation and when toxoplasma diagnosis is in doubt, steroids should always be used in combination with empirical toxoplasma therapy pending definitive diagnosis.

Conclusion

Our case illustrates an important opportunistic infection in the HIV population with an unusual presentation. The relatively high CD4 cell count, the presence of lung cavities which improved with therapy, and the demonstration of toxoplasma cysts in brain tissue both on touch preparation and immunohistochemistry make this case a unique one.

Care providers should be familiar with atypical clinical presentations of toxoplasmosis and the options available to establish the correct diagnosis.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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