Acute Autoimmune Hepatitis, Myositis, and Myasthenic Crisis in a Patient with Thymoma
Authors: Arun Rajan, David Kotlyar, Giuseppe Giaccone
Journal: Journal of Thoracic Oncology (2013)

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 after plasmapheresis. A 42-year-old white woman with a World Health Organization B2/B3, stage IVA thymoma presented with fatigue, dyspnea, and orthopnea. Laboratory workup showed transaminitis (aspartate transaminase 377 U/liter, upper limit of normal [ULN] 34 U/liter; alanine aminotransferase 357 U/liter, ULN 41 U/liter; elevated creatine kinase, 1462 U/liter, ULN 252 U/liter; and lactate dehydrogenase 947 U/liter, ULN 226 U/liter), no serological evidence of hepatitis A, B, or C infection, and absence of anti–smooth muscle and antinuclear antibodies. Hepatic ultrasound showed no metastases and patent veins. The patient's symptoms continued to worsen, and approximately 4 weeks after diagnosis of thymoma, she developed dysarthria, dysphagia, and mental status changes culminating in unresponsiveness, for which intubation and mechanical ventilation were required. 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 because of the life-threatening nature of myasthenic crisis. Serum acetylcholine receptor binding antibody levels were elevated at 4.91 nmol/liter (ULN 0.02 nmol/liter), thus, confirming MG. Plasmapheresis resulted in rapid clinical improvement and near normalization of biochemical parameters but ventilator dependence continued. Pyridostigmine at a dose of 60 mg every 8 hours was started 4 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 before and during administration of chemotherapy. For this purpose, dexamethasone was administered intravenously at a dose of 12 mg once, 1 hour before 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 8 days after completion of plasmapheresis, and the patient came off ventilatory support within 48 hours. Levels of liver enzymes, creatine kinase, and lactate dehydrogenase at key time points are depicted in Figure 1. A computed tomography scan confirmed tumor shrinkage after one cycle of chemotherapy (Fig. 2). The patient received two cycles of chemotherapy during her hospitalization, after which she was discharged. 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 2Computed tomography scan demonstrating an anterior mediastinal mass at baseline (A) and tumor shrinkage 3 weeks after initiation of chemotherapy (B).View Large Image Figure ViewerDownload (PPT) Thymomas are rare tumors with an incidence of 0.13 cases per 100,000 person-years.1Engels EA Epidemiology of thymoma and associated malignancies.J Thorac Oncol. 2010; 5: S260-S265Abstract Full Text Full Text PDF PubMed Scopus (351) Google Scholar Autoimmune disorders occur with thymoma, the most common of which is MG.2Shelly S Agmon-Levin N Altman A Shoenfeld Y Thymoma and autoimmunity.Cell Mol Immunol. 2011; 8: 199-202Crossref PubMed Scopus (136) Google Scholar AIH has also been reported.3Yapali S Oruc N Ilgun S et al.Acute presentation of autoimmune hepatitis in a patient with myasthenia gravis, thymoma, hashimoto thyroiditis and connective tissue disorder.Hepatol Res. 2012; 42: 835-839Crossref PubMed Scopus (13) Google Scholar Up to 7% of patients with thymoma and MG have other paraneoplastic conditions.4Monden Y Uyama T Nakahara K et al.Clinical characteristics and prognosis of myasthenia gravis with other autoimmune diseases.Ann Thorac Surg. 1986; 41: 189-192Abstract Full Text PDF PubMed Scopus (41) Google Scholar 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, although temporary improvement. This case highlights the need to recognize the benefit of rapid initiation of chemotherapy after plasmapheresis in patients with unresectable thymoma to gain durable control of associated autoimmune disorders.