Sézary Syndrome — SCE Dermatology MCQ

Correct answer: E — Leukapheresis of peripheral blood with extracorporeal UVA irradiation of mononuclear cells treated with 8-methoxypsoralen, then reinfusion

Option E (leukapheresis of peripheral blood with extracorporeal UVA irradiation of mononuclear cells treated with 8-methoxypsoralen, then reinfusion) correctly describes ECP. The UK Photopheresis Society consensus statement, endorsed alongside BAD/UK Cutaneous Lymphoma Group guidance, describes ECP as a three-stage process: leukapheresis to collect the buffy coat, photoactivation of these mononuclear cells with 8-methoxypsoralen and UVA outside the body, then re-infusion of the treated cells back to the patient. UVA activates the psoralen to crosslink DNA in the collected lymphocytes, inducing apoptosis of malignant and activated T cells and triggering a systemic immunomodulatory anti-tumour response, without generalised immunosuppression. This makes it the standard first-line systemic therapy for erythrodermic CTCL/Sézary syndrome in UK specialist centres. Why the other options are wrong: A. Plasmapheresis removing immunoglobulins: ECP separates and treats cellular mononuclear cells, not plasma or immunoglobulins; plasmapheresis is used in conditions like myasthenia gravis or TTP, not CTCL. C. Whole-body electron beam therapy: this refers to total skin electron beam therapy (TSEBT), a direct external radiotherapy technique for skin-limited disease, entirely separate from any extracorporeal blood processing. D. UV irradiation of the skin directly: this describes conventional phototherapy (broadband or narrowband UVB) applied to the skin surface, not blood cells processed outside the body. B. Oral PUVA therapy: PUVA combines oral or topical psoralen with UVA exposure of the skin itself, not extracorporeal treatment of leukapheresed blood; it is used for plaque-stage mycosis fungoides rather than erythrodermic Sézary syndrome. Key point: ECP is defined by its extracorporeal, cell-based mechanism, leukapheresis, psoralen-UVA photoactivation of mononuclear cells, then reinfusion, distinguishing it from skin-directed phototherapy, PUVA, radiotherapy, or plasma-based apheresis.

Reference: UK Photopheresis Society consensus statement update (Scarisbrick et al., British Journal of Haematology, 2018): 'Extracorporeal photopheresis involves three stages: (i) leukapheresis; (ii) photoactivation with 8-methoxypsoralen (8-MOP)/UVA; and (iii) re-infusion of buffy coat.' https://onlinelibrary.wiley.com/doi/10.1111/bjh.14537