Severe Acute Orthopnea: Ipilimumab-Induced Bilateral Phrenic Nerve Neuropathy

Abstract

Ipilimumab is a monoclonal antibody used in the treatment of unresectable or metastatic melanoma. Several immune-related adverse events including potential fatal events have been reported following its use. We report a case of a 66-year-old man who presented with severe acute exertional dyspnea and orthopnea following administration of ipilimumab for metastatic melanoma. Although various peripheral neuropathy syndromes associated with ipilimumab have been reported, bilateral phrenic nerve paralysis has not been previously reported. This case also highlights the clinical features of bilateral phrenic nerve neuropathy. Pulmonologists have to be aware of these unusual immune-related respiratory adverse events in patients being treated with monoclonal antibodies.

Unilateral Cervical Polyneuropathies following Concurrent Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer

“…Two-thirds of patients enrolled in a Phase I study of the EGFR inhibitor gefitinib in combination with paclitaxel and radiotherapy were noted to develop severe oral dysesthesia [ 15 ]. In that study, the combination of an EGFR inhibitor appears to have exacerbated the potential neuropathic effects of paclitaxel with radiotherapy, since in previous trials of cetuximab in combination with radiotherapy for HNC, encompassing 227 patients, there were no reported instances of RIBP or other distinct nerve injuries as described in the present case report [ 14 – 16 ].…”

“…Phrenic nerve injury secondary to radiation therapy is rarely described, with only four previously reported cases. Regarding potential contributions from monoclonal antibody therapy, one case describes a patient with bilateral phrenic nerve injury secondary to ipilimumab [ 14 ]. Though the patient presented in this case report received a different monoclonal antibody, cetuximab, further study into potential adverse effects of treatment with monoclonal antibodies may be warranted.…”

A case of progressive orthopnoea and shoulder pain secondary to bilateral diaphragmatic paralysis

“…In later years, it was found to affect other motor nerves, including the phrenic nerve, due to inflammation of the C3-C5 nerve roots and can lead to unilateral or bilateral diaphragmatic paralysis. [1][2][3][4][5] NA is an idiopathic condition, often preceded by a viral or infectious precipitant. Case reports of bilateral phrenic nerve paralysis due to NA after herpes zoster infection and tetanus antitoxin, as well other toxic precipitants such as chemotherapy, have been described.…”

Bilateral Facial Palsy following Ipilimumab Infusion for Melanoma

“…Other reported neuropathies include bilateral phrenic nerve paralysis and sensory neuropathy. 4 Ipilimumab was the likely cause of facial palsy, on the basis of negative workup of other causes and the tight temporal relationship between symptoms and preceding infusions. The differential diagnosis included metastases to the facial nerve root and Lyme disease neuropathy; however, laboratory testing and imaging ruled these causes out.…”

“…Although no other cases of facial nerve palsy have been reported, 1 case described a patient with both peripheral nerve and cranial nerve III neuropathy, including distal extremity weakness and ptosis, who recovered fully with prednisone and by discontinuing the infusion. Other reported neuropathies include bilateral phrenic nerve paralysis and sensory neuropathy 4 …”