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Successful low-dose azathioprine for myasthenia gravis despite hepatopathy from primary sclerosing cholangitis: a case report
© Finsterer and Höflich; licensee BioMed Central Ltd. 2010
Received: 24 January 2010
Accepted: 8 November 2010
Published: 8 November 2010
Although myasthenia gravis is frequently associated with other disorders, it has not been reported together with primary sclerosing cholangitis, complicating the administration of liver-toxic immunosuppressive therapy.
A 73-year-old Caucasian woman with a history of arterial hypertension, thyroid dysfunction, glaucoma, right-sided ptosis and later generalized weakness, was diagnosed with myasthenia gravis. Additionally, primary sclerosing cholangitis was detected, initially prohibiting the administration of immunosuppressants. Despite treatment with steroids and pyridostigmine she repeatedly experienced myasthenic crises. After the fifth crisis and after antibody titers had reached levels > 100 nmol/L during two years of follow-up, it was decided to restart azathioprine. Interestingly, low-dose azathioprine (1.5 mg/kg/day) was well tolerated, had a positive clinical and immunological effect and did not worsen primary sclerosing cholangitis.
Myasthenia gravis may occur together with primary sclerosing cholangitis in the same patient. Mild immunosuppression with azathioprine is feasible and effective in such a patient, without worsening myasthenia gravis or primary sclerosing cholangitis.
Myasthenia gravis (MG) may be due to a genetic defect, intoxication, or most frequently, autoimmune mechanisms . Although autoimmune MG is frequently associated with other autoimmune disorders [2–13], to the best of our knowledge the association of MG with primary sclerosing cholangitis (PSC) has not been reported.
On hospital day 11 she experienced a myasthenic crisis, requiring intubation, intravenous administration of neostigmine and immunoglobulins, and plasmapheresis six times. Resection of the mediastinal tumor on hospital day 13 revealed a thymoma B3, without indication for chemotherapy. After surgery pyridostigmine was restarted but had to be replaced by neostigmine on hospital day 34 due to better efficacy. Azathioprine was initiated on hospital day 34 in a reduced dosage (50 mg/day) because of hepatopathy and increased to 100 mg/day on hospital day 44 (figure 2). On hospital day 47 she experienced a second myasthenic crisis and again required intensive care. On hospital day 57 a third myasthenic crisis manifested with dysphagia, dyspnea, and respiratory failure, again requiring intensive care. On hospital day 72, azathioprine was increased to 150 mg/day while prednisolone remained at 25 mg/day (figure 2). Upon diagnostic work-up for further increase of liver function parameters, magnetic resonance (MR)-cholangiography revealed PSC with negative anti-nuclear antibodies (ANA), smooth-muscle antibodies, anti-mitochondrial antibodies, liver-kidney antibodies, or soluble liver antigen. Ursodesoxycholic acid was given and azathioprine was discontinued (figure 2). At discharge on hospital day 108 she was under prednisolone (15 mg/day), pyridostigmine (360 mg/day), glimepiride (7 mg/day) for mild diabetes, ursodesoxycholic acid (1250 mg/day), calcium, and alendrone (70 mg once a week) for osteoporosis (figure 2). Except for right-sided ptosis, she was symptom-free.
Two months after dismissal AchR-ab reached its lowest level (figure 1) so steroids were reduced to 10 mg/day. At age 72 years, prednisolone was further reduced to 5 mg/day. Six months later she presented with right-sided ptosis, slight weakness, wasting of the thighs, exaggerated patella tendon reflexes and reduced Achilles tendon reflexes. Pyridostigmine was increased to 480 mg/day and prednisolone reduced to 2.5 mg/day. Three months later pyridostigmine was reduced to 360 mg/day without a relapse. At age 73 years she experienced a fourth myasthenic crisis during an infectious disease, requiring intubation and mechanical ventilation. After increase of prednisolone and pyridostigmine she made a full recovery. A fifth myasthenic crisis occurred five months later, which responded simply to switching from pyridostigmine to neostigmine intravenously. At that time it was decided to restart azathioprine in a dosage of 100 mg/day because of recurrent myasthenic crises and maximal elevation of AchR-ab to 117.03 nmol/L (figures 1 and 2). Because of azathioprine-induced elevation of liver function parameters (figure 3) azathioprine had to be reduced to 50 mg/day. At age 74 years corticosteroids were discontinued and azathioprine increased to 75 mg/day and later 87.5 mg/day, without further elevation of liver function parameters. Under this regimen MG did not recur and AchR-ab levels remained low until the last follow-up at age 75 years.
Autoimmune disorders frequently associated with MG.
Diabetes mellitus type 1
Giant cell myocarditis
Primary biliary cirrhosis
Treatment options for primary sclerosing cholangitis.
MG may occur together with PSC in the same patient. Immunosuppression with azathioprine in PSC and MG with progressively increasing high antibody titers is feasible, safe, and effective, even with reduced dosages, provided there is close monitoring of AchR-ab and liver function parameters.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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