Erdheim-Chester disease (ECD) is a rare, slowly progressive non-Langerhans cell histiocytosis that affects bone and multiple viscera. In 2016, the World Health Organization classified it as a distinct entity in the family of histiocytic neoplasms, and less than 1,500 cases are documented in the international literature. The article describes a 49-year-old man with biopsy-confirmed ECD who developed acute suppurative appendicitis. He underwent laparoscopic appendectomy under general anesthesia and was transferred to the intensive care unit due to multiorgan involvement of the ECD. There, he was placed on a multidisciplinary regimen including pulmonary protective ventilation, continuous renal replacement therapy, broad-spectrum antibiotics, granulocyte colony-stimulating factor, and glucocorticoids. These measures resulted in stable respiratory and renal function, and the patient was discharged to the hematology department on postoperative day 10. Patients with ECD are prone to perioperative deterioration due to pulmonary infiltration, refractory hypoxemia, acute kidney injury, and immune paralysis. A successful outcome depends on coordinated multidisciplinary care, accurate hemodynamic and volume management, timely continuous renal replacement therapy, and immunomodulation.