Gastrointestinal: Severe gastritis and colitis leading to gastrointestinal hemorrhage in a patient with drug reaction with eosinophilia and systemic symptoms syndrome

A 15-year-old adolescent male presented with a headache and recurrent fever for 5 months. A magnetic resonance imaging (MRI) of the brain suggested purulent meningitis, and the patient received vancomycin. However, within a month, the patient developed extensive rashes, itching, and skin peeling. Vancomycin was discontinued. Two days later, the patient experienced abdominal pain, watery diarrhea with yellow-green stools (2000–3000 mL/day), and poor appetite. Further examination of the cerebrospinal fluid using next-generation sequencing (NGS) revealed the presence of human herpesvirus 6B (HHV-6B; sequence count: 4426). Then, the patient started to pass bloody stools, generating 2–5 L of watery stools per day. Laboratory tests showed white blood cells of 27.63 × 109/L, eosinophils of 1.5 × 109/L, hemoglobin of 48 g/L, and platelets of 23 × 106/L. Biochemical tests showed elevated levels of total bilirubin, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and serum IgE. Results for human immunodeficiency virus, human parvovirus B19, Clostridium difficile, Epstein–Barr virus, cytomegalovirus, norovirus, Shigella dysenteriae, tuberculosis, blood, and stool cultures were all negative. An abdominal computed tomography (CT) scan showed enlarged gallbladder, splenomegaly, diffuse thickening and swelling of the whole intestinal wall, and multiple enlarged mesenteric and retroperitoneal lymph nodes. Gastroscopy revealed mucosal erosion and ulceration with contact bleeding in the duodenum (Fig. 1a). The colonoscopy showed multiple superficial ulcerations with diffuse mucosal exfoliation and necrosis in the colon (Fig. 1b). Biopsies were not taken due to thrombocytopaenia and the presence of gastrointestinal bleeding at the time of endoscopic examination. Intestinal failure was diagnosed due to the worsening diarrhea. These findings were consistent vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS), involving both cutaneous and gastrointestinal symptoms. By applying the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system,1 the final RegiSCAR score was 7 points, categorizing the patient as a definite case of DRESS syndrome. The therapeutic approach was categorized into three distinct components: (i) nutritional support: The nutritional support primarily involved parenteral nutrition support, complemented by minimal enteral nutrition to potentially facilitate the regeneration of the gastrointestinal mucosa; (ii) anti-infective therapy: The emphasis was placed on the utilization of antifungal agents; and (iii) management of DRESS syndrome and intestinal failure: This included the application of corticosteroids, intravenous immunoglobulin (IVIG), and growth hormones. The patient died due to subsequent severe fungal endocarditis 7 months after the onset of gastrointestinal symptoms. DRESS syndrome, although rare, is a severe and life-threatening cutaneous adverse reaction. It typically occurs 2–6 weeks following exposure to an offending medication and is characterized by severe skin eruptions, fever, eosinophilia, lymphadenopathy, and multi-organ involvement.2 The offending drugs may trigger HHV-6B reactivation, resulting in immune activation and an exaggerated antiviral T-cell response that generates DRESS syndrome. This patient had a history of offending medication use and a prolonged course of life-threatening illness. These clinical findings suggest that DRESS syndrome, rather than primary HHV-6B infection, may be the cause of gastrointestinal hemorrhage and thrombocytopenia in this patient. Gastrointestinal bleeding may result from thrombocytopenia, a known manifestation of DRESS syndrome. However, the underlying cause of thrombocytopenia in DRESS syndrome remains incompletely elucidated. One potential mechanism involves the abnormal immune response triggered by medication, which may contribute to increased platelet destruction and defects in platelet synthesis within the bone marrow. While vancomycin is a common culprit in patients who develop renal complications of DRESS, less is known about gastrointestinal involvement and predilection based on the offending drug.3 When gastrointestinal manifestations appear in the course of DRESS syndrome, an endoscopy examination should be performed to identify gastrointestinal mucosal injury, which could lead to ulceration and mucosal barrier disruption. Early recognition of drug-induced reactions as a causative factor in gastrointestinal mucosal damage serves as a critical step for improving the accuracy of clinical diagnosis.