Pyostomatitis vegetans (PSV) is an uncommon inflammatory disorder of the oral mucosa, frequently associated with inflammatory bowel disease. IgA pemphigus, a rare autoimmune bullous disease, seldom involves mucosal tissues. We present a case of IgA pemphigus initially manifesting as PSV, with subsequent development of pustular lesions on the posterior trunk, neck, back, and perianal region, accompanied by gastrointestinal symptoms and peer reactions. The patient's condition improved following combination therapy with glucocorticoids, thalidomide, and rituximab. The extensive mucosal involvement observed in this case broadens the understanding of the clinical spectrum of IgA pemphigus. This report highlights that PSV may serve as an initial manifestation of IgA pemphigus, which should therefore be considered in the differential diagnosis of such oral lesions. Multidisciplinary management is essential for accurate diagnosis and effective treatment.