Probable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review

Abstract

BackgroundProgressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient’s immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities.Case presentationA 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient’s CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms.ConclusionsWhen neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.

Progressive multifocal leukoencephalopathy in a lung transplant recipient presenting with memory impairment: Case report and literature review

“…This case constitutes the twelfth reported instance of PML after lung transplantation and only the fourth where a confirmatory brain biopsy or autopsy has been performed 4‐12 . It is worthy of discussion because of its rarity and because it powerfully highlights the clinical dilemmas associated with this challenging and highly morbid condition.…”

“…It is now known to affect patients with broad causes of immunocompromise such as those receiving immunosuppression for multiple sclerosis (specifically α‐4 integrin antagonist therapy), lymphoma, leukemia, and autoimmune conditions such as systemic lupus erythematosus. It has also been reported to affect patients after stem cell and solid organ transplantation, although the disease appears very rare after lung transplantation with only eleven cases having been reported 4‐12 …”

Case Report: Central Nervous System Immune Reconstitution Inflammatory Syndrome Related to Bacterial Meningitis

“…On brain biopsy or postmortem examinations, T lymphocytes and macrophages are found predominantly in the parenchyma and perivascular spaces ( 11 ). Brain MRI abnormalities, including new swelling with perilesional and perivascular edema, are often found in CNS-IRIS patients ( 12 ). The lesions might show contrast enhancement on MRI, due to local inflammation and breakdown of the blood–brain barrier ( 13 , 14 ).…”

Management of Multidrug Resistant Infections in Lung Transplant Recipients with Cystic Fibrosis

“… 72 Although it remains very rare after LTx, with only several cases reported and none in CF patients, this demyelinating disease of the central nervous system frequently causes severe morbidity or death and thus, a high index of clinical suspicion should be maintained. 73 , 74 …”