Epiglottic Lesions as the Initial and Primary Presentation of Pemphigus Vulgaris

A 55-year-old man presented to our institution with persistent pharyngolaryngeal pain and ulcerations of the epiglottis. Before presenting to our institution, the patient had sought evaluation at three other hospitals. At the first and second external hospitals, he underwent multiple blood tests, laryngoscopies, and computed tomography scans. He was subsequently diagnosed with chronic pharyngitis and treated with anti-infective therapy; however his symptoms did not improve. He then presented to a third external hospital, where an epiglottic biopsy was interpreted as focal squamous cell carcinoma (SCC). Based on this diagnosis, chemotherapy was initiated (details unavailable). Because his symptoms progressed, he sought further evaluation at our hospital.

At his initial presentation to our hospital, the clinical manifestations were as described above. Routine blood tests were unremarkable. Laryngoscopy revealed that white pseudomembranes covered approximately 70-80% of the epiglottic surface and predominantly involved the lingual surface of the epiglottis (Figure 1a). Narrow-band imaging showed no aberrant vasculature (Figure 1b). Importantly, our pathologists re-reviewed the outside biopsy that had initially been diagnosed as SCC, which showed only squamous epithelial hyperplasia, dysplasia, and lacunar changes in the basal layer (Figure 1d and e). A repeat epiglottic biopsy performed at our hospital also revealed squamous epithelial hyperplasia and dysplasia (Figure 1c). Immunohistochemistry was positive for p63 and partially positive for p53 and Ki-67, findings suggestive of epithelial hyperplasia or dysplasia. Based on the clinical presentation and examination findings, SCC was considered unlikely. Nevertheless, a definitive diagnosis could not be established. Accordingly, he received oral traditional Chinese medicine for mucosal repair, with a 1-month follow-up appointment scheduled.

Figure 1.

Initial examinations and follow-up. (a) White light imaging of laryngoscopy. (b) Narrow-band imaging of laryngoscopy demonstrates no abnormal vascular patterns. (c) Epiglottic biopsy at our hospital revealed focal moderate epithelial dysplasia. (d, e) External biopsy review: squamous epithelial dysplasia and lacunar or blister-like structures in the basal layer. (f) Cephalofacial flaccid bullae and erosions. (g) Persistent epiglottic ulceration with adherent pseudomembrane. (h) Acantholysis (white arrow) and tombstoning of basal keratinocytes (red arrow). (i) One-year follow-up laryngoscopy showed full resolution.

One month later, the patient returned for follow-up evaluation. His pharyngolaryngeal pain and epiglottic ulcerations persisted, accompanied by new oral ulcers and facial bullae (Figure 1f). Given the synchronous mucosal and cutaneous lesions, a dermatology consultation raised suspicion for pemphigus. Additional serological testing for autoantibodies revealed elevated levels of anti-desmoglein (Dsg) 1 (86.50 U/mL) and anti-Dsg 3 (171.30 U/mL). Repeat laryngoscopic examination showed no substantial change compared with the previous findings (Figure 1g). Pathological examination of a repeat biopsy revealed the hallmark feature of suprabasal acantholysis (Figure 1h). Based on these findings, pemphigus vulgaris (PV) was confirmed. Regarding treatment, corticosteroids remain the mainstay of PV treatment. Immunosuppressants are commonly used as steroid-sparing agents to control disease activity and maintain remission.^{1, 2} The patient subsequently received guideline-based treatment with methylprednisolone (10 mg q.d.) plus azathioprine (100 mg q.d.). The methylprednisolone dose was individualized according to disease extent and stability, while azathioprine was added to maintain disease control and reduce cumulative corticosteroid exposure. After more than 1 year of follow-up, his pharyngolaryngeal pain had resolved completely, the oral ulcerations and facial bullous lesions had fully healed, and laryngoscopy showed significant regression of the epiglottic pseudomembrane and ulcers (Figure 1i).

PV is a rare autoimmune blistering disease with an annual incidence of approximately 1-5 per million worldwide.³ It is mediated by immunoglobulin G autoantibodies against Dsg 1 and/or 3, leading to suprabasal acantholysis.⁴ Typical manifestations include flaccid blisters and erosions involving the oral mucosa, chest, back, and head.⁵ However, when PV initially presents as isolated laryngopharyngeal lesions, particularly on the epiglottis, diagnosis can be challenging and delayed. PV is not generally considered a premalignant disorder; however, epithelial dysplasia has rarely been reported in association with PV. Kowalski et al.⁶ described oral and epiglottic dysplasia that was initially suspected to be precancerous before PV was ultimately diagnosed. In the present case, the facial bullous lesions provided important diagnostic clues. Multidisciplinary assessment, anti-Dsg 1 and anti-Dsg 3 antibody testing, and pathologic examination of biopsy specimens are essential. Biopsy remains the diagnostic gold standard, and current guidelines recommend sampling newly formed blisters within 24 hours.⁷