S5821 Bullous Pemphigoid Revealing AMA-Negative PBC-AIH Overlap Syndrome: A Multisystem Autoimmune Diagnosis Anchored by Histology

Introduction: AMA-negative overlap syndromes pose a diagnostic challenge in autoimmune liver disease, particularly when classical serologies are absent. Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) may coexist despite seronegative profiles, necessitating histologic confirmation. This case demonstrates how a concurrent dermatologic autoimmune process—bullous pemphigoid—served as an early systemic clue. Case Description/Methods: A 45-year-old woman presented with progressive jaundice, fatigue, pruritus, and new-onset bullous skin lesions involving the chest, abdomen, and inner thighs. She denied joint pain, fever, or mucosal involvement. On examination, she had icterus, xanthelasma, healing bullae, and a body mass index of 17.5 kg/m². Laboratory studies revealed microcytic anemia, cholestatic liver enzyme elevation, and hypoalbuminemia. Autoimmune panel was notable for high-titer antinuclear antibody, but negative antimitochondrial antibodies (AMA), anti-smooth muscle antibodies, anti-LKM, anti-dsDNA, and anti-Smith antibodies. Abdominal ultrasound showed hepatomegaly and a contracted gallbladder. MRCP excluded biliary obstruction. Skin biopsy confirmed bullous pemphigoid. Liver biopsy demonstrated lymphocytic interface hepatitis with bile duct injury, consistent with PBC–AIH overlap as per Paris criteria. DEXA scan revealed severe osteoporosis (lumbar spine T-score –4.9), attributed to chronic cholestasis. Discussion: This case exemplifies the need for histologic assessment when serologic data is inconclusive but clinical suspicion persists. AMA-negative PBC is well-documented, yet often underdiagnosed without biopsy. The coexistence of bullous pemphigoid highlighted the systemic nature of autoimmune activation. Severe skeletal involvement reinforced the chronicity of the liver disease and the need for metabolic surveillance in cholestatic conditions. In AMA-negative cholestatic liver disease, liver biopsy remains indispensable for establishing overlap syndromes. Dermatologic findings such as bullous pemphigoid may offer an early clue to systemic immune dysfunction. Integration of hepatic pathology, autoimmune markers, and dermatologic context is key to timely diagnosis and intervention.