Neurological

Checkpoint inhibitor-linked mononeuritis multiplex in patients with mesothelioma

A 61-year-old woman with pleural mesothelioma developed a pembrolizumab-associated CD8 + vasculitic mononeuritic multiplex, according to a case report published in Neurology, Neuroimmunology & Neuroinflammation.

While the introduction of immune checkpoint inhibitors has revolutionized cancer treatment, inhibiting T-cell activation can also be linked to immune-related side effects. There is a single report of immune checkpoint inhibitor-associated vasculitic peripheral neuropathy. The current report describes a histologically confirmed pembrolizumab-associated sensorimotor non-systemic vasculitis mononeuritis multiplex in a patient with malignant mesothelioma.

The patient initially received carboplatin / pemetrexed treatment. Pembrolizumab was started later as maintenance therapy, but discontinued after one year because of suspected immune checkpoint inhibitor-associated colitis. However, pembrolizumab was reinstated as the disease progressed and used until multiple cutaneous petechiae appeared. A skin biopsy revealed evidence of small vessel vasculitis, which was suspected to be secondary to immunotherapy.

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Subacute neurological symptoms were reported after 2 weeks as the patient developed bilateral foot fall syndrome, paresis in the right ulnar nerve distribution area, and hypesthesia / allodynia of the feet, right hand, and left thumb. Investigations of the motor nerve conduction showed severe axonal damage in the right median and ulnar nerves as well as the peroneal and tibial nerves.

The neural ultrasound showed fascicular nerve swelling in both the sural and ulnar nerves, suggesting vasculitic neuropathy. Ultrasound-guided biopsy of the sural nerve confirmed small vessel vasculitis with a predominance of CD8 + T cells.

The clinical, electrophysiological, and imaging findings were consistent with the diagnosis of non-systemic vasculitic mononeuritis multiplex. While the treatment of immunotherapy-associated non-systemic vasculitic mononeuritis multiplex is not defined, the study researchers started treatment with high-dose methylprednisolone, followed by cyclophosphamide.

Due to persistent severe allodynia, treatment with pregabalin, amitriptyline, and methadone have been attempted and have shown moderate effectiveness.

“Careful assessment and reporting of rare side effects expand knowledge and understanding of the complex immune network and pathogenesis of neurological ICI [immune checkpoint inhibitor]-related side effects.

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Baldauf MC, Kapauer M., Jörger M., et al. Pembrolizumab-associated CD8 + vasculitic mononeuritis multiplex in a patient with mesothelioma. Neurol Neuroimmunol Neuroinflamm. Published online April 6, 2021. doi: 10.1212 / NXI.0000000000000993

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