Checkpoint Inhibitor-Linked Mononeuritis Multiplex in Patient With Mesothelioma

Micrograph of peritoneal Mesothelioma. Mesothelioma is a rare, aggressive form of cancer that primarily develops in the lining of the lungs (pleural mesothelioma) or the abdomen (peritoneal mesothelioma). Caused by asbestos, mesothelioma has no known cure and has a poor prognosis. Generally, the earlier mesothelioma is diagnosed, the better prognosis a patient has.
A 61 year old woman with pleural mesothelioma developed pembrolizumab-associated CD8+ vasculitic mononeuritic multiplex.

A 61 year old woman with pleural mesothelioma developed 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 care, the inhibition of T-cell activation may also be associated with immune-related adverse effects. There is a single report on immune checkpoint inhibitor-associated vasculitic peripheral neuropathy. The current report describes a histologically proven pembrolizumab-associated sensorimotor nonsystemic vasculitis mononeuritis multiplex in a patient with malignant mesothelioma.

The patient initially received carboplatin/pemetrexed treatment. Pembrolizumab was initiated later as maintenance therapy, but was discontinued after a year due to suspected immune checkpoint inhibitor-related colitis. However, pembrolizumab was reinstated following disease progression and was used until multiple cutaneous petechiae developed. A skin biopsy indicated evidence for small vessel vasculitis suspected to be secondary to the immunotherapy.

After 2 weeks, subacute neurologic symptoms were reported, as the patient developed bilateral foot drop syndrome, paresis in the right ulnar nerve distribution, and hypoesthesia/allodynia of the feet, the right hand, and the left thumb. Motor nerve conduction studies indicated severe axonal damage in the right median and ulnar nerves and both peroneal and tibial nerves.

Nerve ultrasound demonstrated fascicular nerve swelling in both 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, electrophysiology, and imaging findings were compatible with a diagnosis of nonsystemic vasculitic mononeuritis multiplex. While the treatment of immunotherapy-associated nonsystemic vasculitic mononeuritis multiplex is not defined, study researchers initiated treatment with high dose methylprednisolone, followed by cyclophosphamide.

 Due to persistent severe allodynia, treatment with pregabaline, amitriptylin, and methadone was attempted and showed moderate efficacy.

“Careful evaluation and reporting of rare side effects broaden the knowledge and understanding of the complex immune network and the pathogenesis of neurologic ICI [immune checkpoint inhibitor]-related side effects.


Baldauf MC, Kapauer M, Joerger 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