Acute Autoimmune Hepatitis, Myositis and Myasthenic Crisis in a Patient with Thymoma

The concurrent occurrence of autoimmune hepatitis (AIH) and myasthenia gravis (MG) has rarely been reported with thymoma. We describe what we believe is the first reported case of a newly diagnosed unresectable thymoma with acute-onset transaminitis and myasthenic crisis that responded to chemotherapy following plasmapheresis.

A 42 year old white female with a WHO B2/B3, stage IVA thymoma presented with fatigue, dyspnea and orthopnea. Laboratory workup showed transaminitis (AST 377 U/L, upper limit of normal (ULN) 34 U/L; ALT 357 U/L, ULN 41 U/L) elevated creatine kinase (CK 1462 U/L, ULN 252 U/L), and lactate dehydrogenase (LDH 947 U/L, ULN 226 U/L), no serological evidence of hepatitis A, B or C infection and absence of anti-smooth muscle and anti-nuclear antibodies. Hepatic ultrasound showed no metastases and patent veins. The patient’s symptoms continued to worsen and approximately four weeks after diagnosis of thymoma she developed dysarthria, dysphagia and mental status changes culminating in unresponsiveness that needed intubation and mechanical ventilation. Troponin I was elevated at 0.165 ng/ml (ULN 0.045 ng/ml) but a transthoracic echocardiogram was unremarkable. A diagnosis of thymoma-associated myasthenic crisis, acute AIH, myositis and myocarditis was made and plasmapheresis initiated immediately due to the life-threatening nature of myasthenic crisis. Serum acetylcholine receptor binding antibody levels were elevated at 4.91 nmol/L (ULN 0.02 nmol/L), thus confirming MG. Plasmapheresis resulted in rapid clinical improvement and near normalization of biochemical parameters but continued ventilator dependence. Pyridostigmine at a dose of 60 mg every 8 hours was started four days after completion of plasmapheresis to provide symptomatic relief from ptosis and residual myasthenic symptoms. Steroids were not used at any stage during hospitalization or for maintenance therapy except as part of routine antiemetic prophylaxis prior to and during administration of chemotherapy. For this purpose dexamethasone was administered intravenously at a dose of 12 mg once one hour prior to initiation of chemotherapy followed by 4 mg every 12 hours for a total of 6 doses starting the following day. Chemotherapy (cisplatin 50 mg/m², doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m², all administered on day 1 and repeated every 21 days) was started eight days after completion of plasmapheresis and the patient came off ventilator support within 48 hours. Levels of liver enzymes, CK and LDH at key time points are depicted in Figure 1. A CT scan confirmed tumor shrinkage after one cycle of chemotherapy (Figure 2). The patient received two cycles of chemotherapy during her hospitalization following which she was discharged home. She went on to receive an additional four cycles of chemotherapy as an outpatient and achieved a very good partial response with no recurrence of myasthenic symptoms.

Figure 1.

Changes in laboratory parameters at key time points. AST, aspartate aminotransferase; ALT, alanine aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase.

Figure 2.

CT scan demonstrating an anterior mediastinal mass at baseline (A) and tumor shrinkage 3 weeks after initiation of chemotherapy (B).

Thymomas are rare tumors with an incidence of 0.13 cases per 100,000 person-years.¹ Autoimmune disorders occur with thymoma, the most common of which is MG.² AIH has also been reported.³ Upto 7% of patients with thymoma and MG have other paraneoplastic conditions.⁴ Although thymectomy is the preferred treatment modality, not all patients are surgical candidates. Steroid therapy can control AIH but can initially worsen MG and precipitate a myasthenic crisis whereas plasmapheresis can result in significant, albeit temporary improvement. This case highlights the need to recognize the benefit of rapid institution of chemotherapy following plasmapheresis in patients with unresectable thymoma to gain durable control of associated autoimmune disorders.