Severe Hepatitis in a Patient With Undifferentiated Connective Tissue Disease: Diagnostic Uncertainty Between Methotrexate Toxicity and Autoimmune Liver Involvement.

A patient in their mid-20s with a background of undifferentiated connective tissue disease (UCTD) presented with two days of worsening jaundice, pruritus, and vomiting. Methotrexate had been stopped six weeks earlier because of mildly elevated liver enzymes, yet the abnormalities progressed after withdrawal. On examination, there was marked jaundice and a non-specific maculopapular rash involving the limbs and face. Laboratory studies showed alanine aminotransferase (ALT) 1,500 IU/L, aspartate aminotransferase (AST) 1,200 IU/L, and bilirubin 238 µmol/L, with normal international normalised ratio (INR) and renal function. Viral, metabolic, and toxicology screens were negative. Autoimmune tests revealed weakly positive antinuclear antibody (ANA) but no other antibodies, with normal immunoglobulin G (IgG )and complement levels. Imaging excluded obstruction. The rash resolved and liver tests normalised within one week with supportive management alone. This case highlights the diagnostic overlap between methotrexate-induced hepatotoxicity and autoimmune-related liver injury in patients with connective tissue disease. Methotrexate toxicity can sometimes persist or worsen after discontinuation, whereas lupus-related hepatitis often lacks strong serological markers. In this patient, the absence of cytopenias, mucosal ulceration, or raised IgG argued against classic methotrexate toxicity or autoimmune hepatitis. Spontaneous recovery without corticosteroids suggested a transient, self-limiting autoimmune process. Careful clinical correlation, multidisciplinary review, and cautious monitoring can help avoid unnecessary escalation of immunosuppressive therapy in similar presentations.