Background: Progressive multifocal leukocencephalopathy (PML) is a potentially fatal degenerative condition caused by reactivation of the human polyomavirus 2 (JC virus) in immunodeficient individuals. It is well recognised in individuals who have received Rituximab, but patients treated with other immunosuppressants are at risk also (1). Moreover, patients with SLE may be at increased risk, even when they are not taking immunosuppressants (1, 2).

Objectives: Describe the case of a patient with a history of lupus nephritis and cerebral lupus, on long-term Mycophenolate mofetil (MMF) and Prednisolone, diagnosed with PML complicated by immune reconstitution inflammatory syndrome (IRIS).

Methods: Case report.

Results: This patient first presented in 2010 at the age of 18 with ankle swelling and proteinuria. She had high ANA and anti-dsDNA titres, and renal biopsy showed class IV lupus nephritis. She went into remission on high dose Prednisolone and MMF and elected to stop her MMF. Four months later, she developed behaviour changes and worsening proteinuria. MRI showed a mild high signal lesion in the right cerebral hemisphere, and she was diagnosed with cerebral lupus. She recovered after treatment with IV methylprednisolone and MMF. Over the subsequent eight years, she had three flares of her lupus nephritis, with repeat biopsies in 2013 and 2018 showing active proliferative (class IVA) glomerulonephritis. Consequently she was treated with varying doses of oral Prednisolone and MMF for most of this period. She never received any B-cell depleting therapies.

In October 2020, she presented to A&E with numbness in her left face and down her left arm and leg. MRI demonstrated signal abnormalities in her right hemisphere, involving the cortex, white matter and leptomeninges. She was lymphopenic (0.58x10^9/L) with a low CD4 count of 136 cells/uL (normal range 620-1990 cells/uL). A recent dsDNA had risen to 70 IU/ml. Her cerebrospinal fluid revealed mildly raised white cells and a weakly positive JC virus PCR. The differential diagnoses included cerebral lupus, opportunistic infection and malignancy. During this period of diagnostic uncertainty, she was treated with an increased dose of oral Prednisolone and plasma exchange. She went on to have a brain biopsy that showed peri-vascular lymphocytic infiltration and JC virus was present in high copy numbers in the brain tissue (49221.8 IU/mL), confirming a diagnosis of PML. Her MMF was stopped but she continued a low dose Prednisolone with the addition of Hydroxychloroquine.

She was re-admitted two weeks after discharge in December 2020 with a right-sided headache, left facial weakness and loss of dexterity in her left hand. MRI showed evidence of IRIS in the right hemisphere with cerebral oedema causing midline shift. She was treated with IV Dexamethasone then Prednisolone 30 mg daily, with a gradual taper over a year.

She has made a good recovery with minimal neurological deficit; she had recurrent seizures which responded well to anticonvulsant therapy. Her SLE has not flared.

Conclusion: This describes a case of PML in the context of longstanding lupus nephritis, treated with prednisolone and MMF. Her longstanding lymphopenia with low CD4 counts were attributed to the combined consequences of active lupus and her cumulative immunosuppressive burden. CD4 lymphopenia is associated with PML in the HIV population, and may provide information about which patients on immunosuppressive treatments are at risk of developing PML (3). However, not enough is known to routinely screen patients and the counts of other lymphocyte subsets are likely to be important too.

The case highlights that PML can be associated with different immunosuppressants, other than B-cell depletion. The prompt diagnosis, facilitated by brain biopsy, and appropriate management led to a good medium-term outcome for this patient, showing that PML is eminently survivable.

REFERENCES:

[1]Calabrese LH, Molloy ES. ARD 2008;67:iii64-iii65

[2]Henegar CE et al. Lupus 2016;25(6):617-26

[3]Mills EA, Mao-Draayer Y. Front Immunol 2018;9:138

Disclosure of Interests: None declared