015 Giant cell hepatitis with CTD and ILD: mycophenolate mofetil treating an elusive multi system disease

Abstract

Background: Mycophenolate mofetil (MMF) is an immunomodulator used to treat several autoimmune diseases. We present a case of its efficacious role in a male with giant cell hepatitis, interstitial lung disease and undifferentiated connective tissue disorder with triple positive antiphospholipid antibodies. Methods: Please see the results section. Results: A 68-year-old male with multiple sclerosis presented to hepatology department with year long history of stably deranged liver function tests. His peak ALP was 828 with ALT of 141. He underwent a range of investigations including liver imaging, antibodies and viral screen which were all unremarkable. Hence a liver biopsy was organised which confirmed giant cell hepatitis - an unusual finding in an adult. Consequently, he underwent further screening including EBV, CMV, Hep A and E and parvovirus PCR and serology testing which were all negative. In order to exclude an occult neoplasm, a CT scan of was organised which incidentally revealed NSIP. His lung function tests showed restrictive pattern with low transfer factor. Echocardiogram showed post-capillary pulmonary hypertension with PA pressure of 38-40mm of Hg. Antibody testing showed strongly positive ANA in homogeneous pattern with anti PM-SCL antibody. Hence he was referred to our unit. Clinical picture was in keeping with likely undifferentiated connective tissue disease with polyarthralgia (no synovitis), early morning stiffness, and Raynaud's and nailfold infarcts with capillaritis on nail bed examination. Further testing confirmed triple positive antiphospholipid antibodies. His ESR was also elevated at 46mm/hr. Rest of the autoimmune screen was negative. In view of multisystem involvement with rheumatic symptoms, hydroxychloroquine 200mg twice daily was commenced. There was no improvement demonstrated at three months review. Hence MMF was initiated with gradual uptitration to 15mg/kg/day. Within six weeks, good improvement was noticed with resolution of nail-fold infarcts and arthralgias. ESR dropped to 30mm/hr. Both ALP and ALT improved to 384 and 71 respectively. A year later he remains well with no new symptoms. His cough and HRCT scan of chest improved as well. Conclusion: To our knowledge, this is the only report of three apparently different diagnoses responding well to MMF. Giant cell hepatitis (GCH) is highly uncommon in adults. Latest review found only a 100 cases reported worldwide. Up to 40% of these had an association with autoimmune disease with autoimmune hepatitis being the most common. There are no reports of antiphospholipid antibodies or interstitial lung disease in this context. MMF has not been previously used in this scenario however it was chosen for its broad impact on suppressing both T and B cell lineages which are implicated in all the concerned disease processes in our patient. Our case underscores the significance of careful evaluation of a challenging disease overlap and the successful role of MMF in this setting. Disclosures: M.K.N has received honoraria and research support of less than £1000 from Novartis and Celgene.