Phytosterolemia-associated histiocytosis as a diagnostic challenge

Phytosterolemia (MIM#210250, Orpha:2882) is a rare inherited disorder characterized by the accumulation of plant sterols. Typical clinical manifestations include cutaneous and tendon xanthomas, premature coronary artery disease, thrombocytopenia, anemia, and arthralgia. We describe a 30-year-old male patient with notable dyslipidemia who presented with signs and symptoms mimicking both Takayasu arteritis and a histiocytic tumor. The diagnosis of phytosterolemia was confirmed by detecting a pathogenic homozygous variant, c.1083G>A (p.Trp361Ter), in the ABCG8 gene. A coinciding systemic inflammatory process, histiocytosis, and phytosterolemia were considered to be interconnected. During the diagnostic process, significant coronary artery disease with ischemic sequelae was identified and routinely treated. Avoiding dietary plant sterols, in combination with ezetimibe and rosuvastatin, effectively corrected dyslipidemia. Despite targeted treatments, C-reactive protein and the erythrocyte sedimentation rate remained elevated, and the patient felt subjectively ill without a considerable prednisolone dose until treatment with interleukin-6 receptor antagonist tocilizumab was initiated. This case suggests that an extreme plant sterol excess may trigger severe, life-threatening inflammation, and highlights the importance of considering phytosterolemia in young patients with unexplained dyslipidemia and systemic inflammatory disease.