Introduction: In patients with acute severe ulcerative colitis (ASUC) undergoing rescue therapy with cyclosporine and steroids, new-onset odynophagia is an ominous sign. Differentiating between drug-induced injury, Candida, CMV, and Herpes Simplex Virus (HSV) is critical but endoscopically challenging. We present a case illustrating the distinct "coalescing geographic" pattern of severe HSV esophagitis and the importance of targeted biopsy sampling.

Case Description: A 43-year-old female with extensive ulcerative colitis was admitted for a severe corticosteroid-refractory flare. Rescue therapy with intravenous cyclosporine was initiated. During hospitalization, she developed acute, intense odynophagia.

Urgent gastroscopy revealed a striking pathology in the mid-esophagus (31–37 cm from incisors). Unlike the discrete plaques of Candida or the deep, punched-out ulcers typically seen in CMV, the mucosa exhibited multiple flat, geographic ulcerations. These lesions were non-fibrinous with an erythematous base and showed a clear tendency to coalesce, resulting in circumferential involvement of the esophageal lumen. The distinct lack of raised plaques or pill fragments shifted the suspicion toward a viral etiology.

Crucially, biopsies were targeted at the raised margins of the ulcers rather than the necrotic center. Histopathology revealed multinucleated giant cells with nuclear molding and "ground-glass" chromatin (Cowdry type A bodies). Immunohistochemistry confirmed Herpes Simplex Virus Type 1 (HSV-1). Treatment with acyclovir resulted in rapid symptom resolution.

Conclusion: This case highlights two essential learning points for the endoscopist managing immunosuppressed IBD patients. First, the endoscopic phenotype of HSV esophagitis evolves from vesicles to diffuse, coalescing geographic ulcers with friable borders, mimicking caustic or pill-induced injury. Second, diagnostic yield depends on technique: unlike CMV (which resides in the ulcer base), HSV infects the squamous epithelium at the ulcer margins. Recognizing this pattern ensures correct biopsy targeting and avoids diagnostic delay in the critical setting of ASUC.