A 41-year-old man with oral pemphigus vulgaris (PV) presented to our clinic with a history of no response to numerous immunosuppressant agents and was referred for extracorporeal photopheresis (ECP) therapy. Although the patient underwent a high-intensity ECP regimen for 5 months, which included two different photopheresis systems, his oral dysesthesia continued to interfere with oral intake, leading to continued weight loss and other adverse events. The intervention was associated with changes in several immune cell subpopulations without modifying the anti-epidermal antibody titers, aligned with his poor clinical outcome. To the best of the authors' knowledge, this is the first report to examine immunophenotyping of a PV patient who was refractory to previous immunosuppression and recalcitrant to high-intensity ECP therapy. | INTRODUC TI ONPemphigus diseases are chronic, autoimmune blistering disorders that can be life-threatening if not properly diagnosed and treated.Autoantibodies directed against desmosomal adhesion proteins, desmoglein (Dsg)-1 and Dsg-3, are critical in its etiopathogenesis.These diseases are diagnosed based on the clinical features as well as IgG and/or complement C3 deposits at the keratinocyte membrane: This is detected by direct immunofluorescence microscopy and a perilesional biopsy, with serum anti-Dsg-1 or anti-Dsg-3 antibodies. 1 The most common forms are pemphigus vulgaris (PV), which often arises with mucosal involvement, and pemphigus foliaceus, characterized by predominant skin lesions. 1 Pemphigus treatments include corticosteroids and several immunosuppressant agents, but some patients, especially those with severe variants, are still refractory to them. In these cases, rational approaches such as therapeutic plasma exchange (TPE), immunoadsorption, or extracorporeal photopheresis (ECP) have low-quality supporting evidence and weak strength in grading recommendations. 2,3