Pembrolizumab-induced Myasthenia Gravis-like Disorder, Ocular Myositis, and Hepatitis

A Case Report

Chia-Yi Tian; Yang-Hao Ou; Shih-Liang Chang; Chih-Ming Lin


J Med Case Reports. 2021;15(244) 

In This Article

Case Presentation

A 75-year-old Taiwanese female presented with painless hematuria and unilateral left leg edema. Her underlying conditions include type 2 diabetes mellitus, hyperlipidemia, and hypertension. Initial assessment by the urologist diagnosed her with urothelial carcinoma of the left ureter, for which she underwent left nephroureterectomy. However, the surgeon discovered partial nonresectable tumors on the pelvic wall and upgraded her tumor staging to pT4N2. She received five cycles of concurrent chemoradiotherapy (6000 cGy/30 fx) with cisplatin and gemcitabine after the surgery. Because she responded poorly to cisplatin-based therapy and the tumor cells tested positive for PD-L1 (>5%), she was started on pembrolizumab (200 mg) once every three weeks (Figure 1).

Figure 1.

This figure shows the time course of the patient presented. She was started on pembrolizumab 200 mg every three weeks from September 24, 2019, and presented with neuroinflammatory adverse effect 2 weeks later. The patient received pulse therapy with 1000 mg methylprednisolone intravenous daily after admission. Because of improvement in adverse effect, she was discharged with oral prednisolone 15 mg twice daily.

She presented to the neurology clinic with an acute onset of bilateral ptosis 16 days after her first infusion of pembrolizumab. Neurological examination demonstrated that she developed complete bilateral ptosis (right ptosis developed one day before left ptosis) without noticeable diurnal change. Extraocular muscle movement (EOM) showed all-direction limitation with vertical and mild adduction sparing. Symmetric pupil reflex was reactive, and no diplopia, orbital pain, chemosis of the conjunctiva, proptosis, facial numbness, muscle pain, or dyspnea were noted. Additionally, there was no bulbar, extremity, or axial involvement.

Laboratory data showed elevated liver enzymes (alanine aminotransferase 163 IU/L, aspartate aminotransferase 258 IU/L) and creatine phosphokinase level (4817 IU/L). Her liver enzymes were within normal range one week before the onset of symptoms. Erythrocyte sedimentation rate and thyroid function were normal. Autoimmune antibodies were negative for the anti-acetylcholine receptor, anti-striated muscle, and anti-muscle-specific kinase antibodies. Gadolinium-enhanced magnetic resonance imaging (MRI) found no evidence of inflammatory, infection, or mass lesions, especially in her orbital region (Figures 2, 3). We also performed a cerebrospinal fluid analysis to rule out neuromuscular junction disorders, paraneoplastic disorders, and peripheral neuropathies. Repetitive stimulation test (3 Hz, abductor digiti minimi (ADM), trapezius, unable for eye because of lack of technical capabilities), ice pack test, and computed tomography of the chest and mediastinum were unremarkable.

Figure 2.

Gadolinium-enhanced T1-weighted MRI image of bilateral orbicularis oculi muscle, coronal view. Showing no abnormal mass lesions or enhancement

Figure 3.

Gadolinium-enhanced T1-weighted MRI image showing no abnormal mass lesions or enhancement within the cavernous sinus, axial view

After admission, she was treated with pyridostigmine 120 mg daily because of suspected myasthenia gravis; however, it was ineffective. Thus, we commenced methylprednisolone pulse therapy (1000 mg intravenous daily for 4 days) for pembrolizumab-induced neuroinflammatory symptoms (CTCAE grade III). The patient's ptosis and EOM improved gradually, and her liver enzymes returned to baseline upon follow-up (CTCAE grade I). She was then discharged with oral prednisolone 15 mg twice daily. Because of this event, her urologist held the pembrolizumab treatment, and she was subsequently lost to follow-up.

Three months later, the patient was readmitted to the oncology ward for progression of urothelial cancer, showing lung, liver, and abdomen metastasis with severe obstructive ileus (Figure 4). After careful consideration, pembrolizumab was restarted as a last resort with the continuation of oral prednisolone 15 mg twice daily. Two weeks after the second infusion of pembrolizumab, no apparent signs of ptosis, EOM limitation, or other neuroinflammatory symptoms were found.

Figure 4.

CT scan of the abdomen with/without contrast, showing distended colon with obstruction at the sigmoid colon. Increased infiltrative soft tissues near the left external iliac vessels favoring tumor metastasis (white arrow). Solid nodule in the liver (white arrow head) also suggestive of metastasis