Minocycline is a second-generation tetracycline commonly used to treat acne vulgaris. Long-term treatment with minocycline has been associated with severe adverse effects, including autoimmune and hypersensitivity reactions.8 Minocycline-associated hepatotoxicity can be due to a systemic hypersensitivity reaction, occurring within a few weeks of therapy initiation, whereas autoimmune hepatitis manifests after a year or more of exposure to the medication (as in this case). Patients may present acutely several months after starting the medication, with symptoms of jaundice, fatigue, and/or joint aches. The acute liver injury is typically self-limited and often resolves with cessation of the drug. However, patients may require corticosteroids and immunosuppressive therapy.
Which is it? Histologically, drug-induced autoimmune hepatitis is indistinguishable from idiopathic autoimmune hepatitis.3 The estimated incidence of idiopathic autoimmune liver disease ranges from 0.7 to 2 out of 100,000 population.9 A systematic review of the literature identified 65 reported cases of liver damage associated with minocycline specifically.1
In this case, given the patient’s 2-year history of minocycline use, it is possible that she developed an acute presentation of autoimmune hepatitis. With drug-induced autoimmune liver injury, complete resolution occurs after withdrawal of the offending medication, and a response to corticosteroid therapy supports the diagnosis. Recurrence of signs or symptoms following corticosteroid cessation may indicate idiopathic autoimmune hepatitis as opposed to a drug-induced form.2
Our patient was started on steroid and immunomodulator therapy, with prednisone 40 mg/d and mycophenolate 250 mg bid. At follow-up with Gastroenterology, the patient’s symptoms and liver function test results had improved significantly (AST, 27 U/L; ALT, 14 U/L; alkaline phosphatase, 51 U/L; and total bilirubin, 0.4 µmol/L). The patient was continued on a prednisone taper while simultaneously titrating mycophenolate. The ultimate plan of care included continuing mycophenolate for a total of 4 to 5 years.
THE TAKEAWAY
During evaluation of a patient with new-onset liver disease, it is important to inquire about prescription medications, drugs, vitamins, and herbal supplements as possible contributors to the disease process. This case highlights the importance of monitoring patients while on minocycline and of weighing the risks vs benefits of long-term therapy. It has been suggested that liver enzymes be tested before therapy initiation and about every 3 months during long-term antibiotic treatment.4 Careful consideration and caution should be taken prior to the initiation of medications that have been linked to rare, but important, adverse reactions.
ACKNOWLEDGEMENT
The authors would like to thank Frank Bauer, MD, and Eva Sotil, MD, for their contributions to this case presentation.
CORRESPONDENCE
Andrea Gillis, DO, Asylum Hill Family Medicine Center, 99 Woodland Street, Hartford, CT 06105; andrea.gillis@ trinityhealthofne.org