Fatal granulomatous amoebic encephalitis caused by Acanthamoeba in a newly diagnosed patient with systemic lupus erythematosus
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.173662
Source of Support: None, Conflict of Interest: None
Granulomatous amoebic encephalitis (GAE) caused by certain species belonging to the genus Acanthamoeba, Balamuthia, or Naegleria presents as a subacute or chronic illness. Amoebic encephalitis caused by Acanthamoeba is seen more often in immunosuppressed individuals. Thus, it may often be associated with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), organ transplantation, administration of steroids and systemic lupus erythematosus (SLE). The clinical progression is rapid, most often leading on to mortality of the patients. The diagnosis in most of these patients is established on postmortem examination. We describe a case of fatal granulomatous amoebic encephalitis in a patient recently diagnosed to be having SLE, who was receiving corticosteroids, cyclophosphamide, methotrexate, and hydroxychloroquine. The patient presented in an altered sensorium and expired after being hospitalized for 6 days. Postmortem examination of the brain showed extensive areas of necrosis and neutrophilic infiltrate with trophozoites and cysts of Acanthamoeba.
Keywords: Acanthamoeba; autopsy; meningoencephalitis; trophozoites and cysts
Amoebic encephalitis caused by Acanthamoeba is seen more often in immunosuppressed individuals. Thus, it is often associated with HIV/AIDS, organ transplantation, steroids and systemic lupus erythematosus (SLE)., The clinical progression is rapid with almost certain mortality. The diagnosis in most of these patients is established on the autopsy examination.
We describe a case of fatal granulomatous amoebic encephalitis in a patient suffering from SLE who was on immunosuppressive treatment.
A 28-year-old male patient presented with a low-grade fever, joint pains, and generalized bodyache for a period of 3 months. He was positive for antinuclear antibody (ANA) and anti–double-stranded deoxyribonucleic acid (dsDNA) and was diagnosed to be having SLE. He had associated hypothyroidism, serositis, and oral candidiasis. Therapy with prednisolone, hydroxychloroquine, and methotrexate was initiated. Approximately 2 months after the initiation of treatment, he complained of intermittent dull-aching headache and restricted eye movements. He was given pulse methylprednisolone therapy; however, the symptoms did not improve. The patient's condition worsened and he was referred to our hospital.
At admission, the patient was febrile, disoriented, and drowsy, arousable only to painful stimulus. He had neck stiffness. He was able to localize pain and was moving all his limbs equally. He also had facial asymmetry and right upper motor neuron facial palsy. No seizures or involuntary movements were observed. Both right and left pupils were nonreactive to light. The extra-ocular movements were restricted, and no doll's eye reflex was noted. A left eyelid swelling was observed with chemosis and discharge. Fundus examination was normal. Neck stiffness and nystagmus were absent. Spasticity of all four limbs was observed with a power of grade 3/5. Deep tendon reflexes at all joints were 2+. Bilateral plantars were equivocal. Sensory examination showed that he was perceiving pain on both sides equally. The cerebellar signs were negative.
Magnetic resonance imaging (MRI) of the brain showed multiple hyperintensities situated in the left parieto-occipital gray-–white matter junctional region, bilateral frontal subcortical area and the deep white matter, left caudate nucleus, internal capsule, left temporal white matter, dorsal medulla, and middle cerebellar peduncle. The lesions increased in number over a period of 1 month, and the sequential MRI features at the onset of symptoms and at hospital admission are shown in [Figure 1].
The routine hemogram was normal along with a raised ESR (60 mm/h) and active urine sediments. Proteinuria was 2.8 g/24 h. Cerebrospinal fluid (CSF) examination revealed lymphocytic pleocytosis. The CSF glucose (37 mg/dL) and chloride levels were normal, and the protein level was increased (125 mg/dL). Blood and CSF cultures and special stains for bacteria, mycobacteria, and fungi were negative. Serum anti-Smith antibodies were strongly positive along with positive ANA. Serum antineutrophil cytoplasmic antibodies (ANCA) were negative. He was given pulse methylprednisolone therapy with a working diagnosis of central nervous system (CNS) vasculitis. The patient's condition progressively deteriorated, and he succumbed within 6 days of hospital stay.
A complete body autopsy was consented for and was performed within 4 hours of death. The organs were in normal anatomical position, and no free fluid was present in any of the body cavities.
After 3 weeks of fixation, the brain weighed 1500 g with hazy and opaque meninges. The left occipital lobe was necrotic. Coronal sections showed extensive distortion of the left occipital lobe and necrosis extending into the left lateral ventricle. Additional necrotic areas were identified in bilateral parietal cortices. Subfalcine herniation was apparent [Figure 2].
The left lower lobe of the lung was consolidated. The other solid organs, including liver, spleen, and kidneys were unremarkable.
Sections from the brain showed large areas of hemorrhage and necrosis. Dense vasocentric neutrophilic infiltrate was seen surrounding the small vessels in the cerebral cortex. Admixed with the inflammatory infiltrate were trophozoites and cysts of Acanthamoeba, some forming ill-defined granulomas. Sections from the pons, cerebellum, and other parts of the brain were essentially normal. The same parasitic forms were also seen in the alveolar microabscesses of the lung. The trophozoites were highlighted on periodic acid-Schiff (PAS) stain [Figure 2].
The microscopic examination of other organs revealed chronic venous congestion in the liver and onion-skin appearance of the splenic vessels. The sections from the kidney showed diffuse endocapillary proliferation of the glomeruli with wire loops and hyaline thrombi. These features were consistent with class IV lupus nephritis.
Granulomatous amoebic encephalitis (GAE) caused by certain species belonging to the genus Acanthamoeba, Balamuthia, or Naegleria presents as a subacute or chronic illness.Acanthamoeba are ubiquitous in the soil and water, and the underlying immunosuppression facilitates the spread of the disease in humans. Corticosteroids and other immunosuppressive drugs perhaps facilitated the development of meningoencephalitis in our patient. The presence of the parasite in the lung was probably the primary source of infection, which could have been acquired through inhalation.
Various reports have been published on the development of meningoencephalitis due to Acanthamoeba in SLE patients.,,,,,,, A PubMed search for Acanthamoeba in SLE patients revealed eight such reports in the world literature. The summary of all these cases is given in [Table 1]. The patients were in the varying age-groups being treated with immunosuppressant drugs, and all of them succumbed to meningoencephalitis.
Vasculitis of the CNS was the primary clinical diagnosis in this patient owing to systemic disease activity, high titers of antibodies, and predominant involvement of the subcortical white matter on imaging. Vasculitis in lupus presents as small-vessel vasculitis leading to microinfarcts and hemorrhages. It is a rare manifestation of SLE, and the incidence in postmortem series is less than 10%., However, failure to respond to intravenous steroids with rapid deterioration is unlikely in vasculitis, perhaps being a point to search for an alternate diagnosis.
In the absence of classic clinical or radiologic features, the diagnosis is essentially based on histopathology. Identification of the exact species of the free-living amoebae is also important. The diagnosis of amoebic meningoencephalitis is essentially based on histopathologic examination. The presence of cyst forms of the parasites in tissues excluded the possibility of Naegleria fowleri infection because patients typically die before trophozoites can become encysted. Guarner et al., have reported immunohistochemical assays as an important measure to identify the exact genus of the amoeba, as there can be considerable morphologic overlap among all of these species. Immunohistochemistry helps in identifying the parasite in necrotic foci and within macrophages, and in differentiating them from macrophages.
The presence of a wrinkled double-walled cyst is characteristic of the Acanthamoeba species. Other modalities for the early diagnosis include CSF microscopy, polymerase chain reaction (PCR) for detection of Acanthamoeba 18S rDNA, and serologic evaluation of the antibody titer.
An optimal antimicrobial therapy is lacking even when the infection is suspected/detected early during hospital admission. Various agents such as ketoconazole, pentamidine, polymyxin, trimethoprim–sulfamethoxazole, sulfadiazine, flucytosine, amphotericin B, and rifampin have been shown to be active against Acanthamoeba. Some reports mention a successful outcome after the initiation of these drug therapies in Acanthamoeba meningitis as well as in disseminated infection.,
In conclusion, we would like to reiterate that the differential diagnosis should include granulomatous amoebic encephalitis among patients being treated for acute/subacute/persisting CNS illnesses, especially when the patient is immunocompromised.
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[Figure 1], [Figure 2]