We read with great interest the study report of Lim and associates regarding uveitis in patients with autoimmune hepatitis (AIH). They reported a multicenter, retrospective, observational study of 7 patients with AIH and uveitis.

We have some comments about diagnostic difficulties of patients with AIH and uveitis. Rodriguez and associates evaluated 1237 patients with uveitis and systemic lupus erythematosus (SLE) was found 59 patients (4.8%). Some studies also implicated SLE as a rare cause of uveitis. Although SLE and AIH are different entities, they have very similar features, such as presence of polyarthralgia, hypergammaglobulinemia, positive anti-nuclear and anti–smooth muscle antibody, anti-double-stranded DNA, anti-ribonucleoprotein, and sex predominance. On the other hand, primary Sjögren syndrome (pSS) is also a cause of uveitis. Carbone and associates evaluated 64 patients with uveitis and pSS was observed in 2 of them (3.13%). Liver involvement is considered to be the most common non-exocrine feature in pSS, and in some studies AIH is reported as a most common cause of liver enzyme abnormality in patients with pSS. Based on these findings patients with AIH and uveitis should be evaluated carefully for possible coexistence of SLE and pSS. Specific histologic and clinical features can help to differentiate AIH from SLE and pSS.

Methotrexate is a commonly used drug in oncologic, dermatologic, and rheumatic diseases. Hepatotoxicity is an important side effect attributed to this drug, and close follow-up of patients is recommended. In the study by Lim and associates, 3 patients were under methotrexate therapy before the diagnosis of AIH and methotrexate ceased after diagnosis of AIH. We agree with the authors that according to the current literature methotrexate does not induce AIH, but it may lead to advanced fibrosis or cirrhosis, even in patients without other risk factors such as excess alcohol, fatty liver, or coincidental viral hepatitis. Also, development of drug-induced hepatitis with accompanying autoimmune features is the other possible side effect. At this time it is difficult to distinguish between AIH and drug-induced hepatitis, even with biopsy findings. Here, 2 of 3 patients had not scored for diagnosis of AIH. So, with these findings we think that diagnostic confusion is inevitable.

In the study, 1 patient was treated with infliximab for uveitis before the diagnosis of AIH. The development of drug-induced AIH is possible in this patient. Tobon and associates reported a patient diagnosed with autoimmune hepatitis after 12 infliximab infusions; also, some cases have been reported about this effect of infliximab in the literature.

In conclusion, the rarity of both conditions is the biggest limitation of large studies. It is difficult to draw a definitive conclusion about coexistence of AIH and uveitis based on the reported 9 cases. We think that the association of AIH and uveitis seems neither real nor coincidental; maybe somewhere between the real and coincidental is a more correct definition for this situation.