Sézary syndrome

Sézary syndrome (SS) is a rare and aggressive form of cutaneous T-cell lymphoma (CTCL), classified as a leukemic variant of mycosis fungoides. It is characterized by a triad of clinical features: generalized erythroderma (widespread reddening of the skin covering more than 80% of the body surface area), lymphadenopathy (enlarged lymph nodes), and the presence of malignant T-lymphocytes with cerebriform (convoluted) nuclei — known as Sézary cells — circulating in the peripheral blood. The disease primarily affects the skin, lymph nodes, and blood, but can also involve other organs as it progresses. Patients typically present with intense, debilitating pruritus (itching), diffuse skin redness, scaling, and skin thickening (lichenification). Additional symptoms may include alopecia (hair loss), nail dystrophy, ectropion (outward turning of the eyelids), palmoplantar keratoderma (thickening of the skin on palms and soles), and edema. The disease predominantly affects older adults, with a median age of onset in the sixth to seventh decade of life. Because the immune system is significantly compromised, patients are susceptible to secondary infections, which represent a major cause of morbidity and mortality. Treatment of Sézary syndrome is challenging and typically involves a multimodal approach. First-line therapies include extracorporeal photopheresis (EPC), low-dose methotrexate, interferon-alpha, and skin-directed therapies such as total skin electron beam therapy. Systemic chemotherapy may be used in refractory cases but is generally associated with limited durable responses. Newer targeted agents, including mogamulizumab (an anti-CCR4 monoclonal antibody), brentuximab vedotin, and histone deacetylase inhibitors (such as vorinostat and romidepsin), have expanded the treatment landscape. Allogeneic stem cell transplantation may be considered in select younger patients with aggressive disease. Despite treatment advances, Sézary syndrome carries a poor prognosis, with a median survival of approximately 2–4 years from diagnosis.

Common questions about Sézary syndrome