Sézary syndrome is an aggressive leukemic variant of CTCL characterized by erythroderma, generalized lymphadenopathy, and malignant T‑cell (Sézary cell) circulation. It carries a poorer prognosis than classic MF and requires systemic therapy, often multimodal, with a focus on controlling pruritus, infections, and quality of life.
Epidemiology and Pathobiology
- Typically presents in older adults; male predominance.
- Clonal malignant CD4+ T cells with skin-homing phenotype (CCR4, CCR7, CLA); immune dysregulation predisposes to infections.
Clinical Features
- Diffuse erythroderma involving >80% body surface area with scaling, lichenification, fissuring.
- Intense pruritus, alopecia (scalp, eyebrows), palmoplantar keratoderma, nail dystrophy, ectropion.
- Generalized lymphadenopathy and constitutional symptoms.
- Secondary infections (bacterial, viral, fungal) are common.
Diagnosis
- Peripheral blood: Sézary cells (cerebriform nuclei) on smear; flow cytometry showing expanded aberrant CD4+ population with loss of CD7 and/or CD26; high CD4:CD8 ratio.
- TCR gene rearrangement demonstrating identical clones in skin, blood, and often nodes.
- Skin biopsy compatible with erythrodermic CTCL.
- Staging: TNMB with B2 blood involvement defining SS; evaluate nodes (excisional biopsy if suspicious) and imaging as indicated; baseline LDH.
Management
- Systemic therapy, frequently in combination:
- Mogamulizumab (anti-CCR4): active in blood/skin disease; infusion reactions and risk of graft-versus-host disease if transplant planned (washout before allo-HCT).
- Extracorporeal photopheresis (ECP): cornerstone for erythroderma with blood involvement; often combined with interferon-α and/or bexarotene.
- Interferon-α and retinoids (bexarotene) as immunomodulatory backbone.
- HDAC inhibitors (romidepsin, vorinostat) for refractory disease.
- Low-dose methotrexate or pralatrexate in select cases.
- Immune checkpoint inhibitors in clinical trials or selected refractory cases.
- Skin-directed adjuncts: topical steroids, mechlorethamine, NB-UVB/PUVA for symptom control.
- Infection prophylaxis and management: consider HSV/VZV prophylaxis with certain agents; prompt treatment of cellulitis/impetiginization; Staphylococcus decolonization if recurrent.
- Allogeneic hematopoietic cell transplantation:
- Consider in eligible patients after achieving disease control; potential for durable remission/cure; balance with treatment-related risks.
Supportive Measures
- Aggressive antipruritic regimens (gabapentinoids, mirtazapine, doxepin), emollients, wet wraps.
- Thermoregulation and fluid/electrolyte management in severe erythroderma.
- Psychosocial support and multidisciplinary care.
Prognosis
- Generally poor compared with early MF; median survival varies (often 3–5 years) but improving with modern therapies. Adverse factors: high Sézary count, elevated LDH, extensive nodal/visceral disease, infections.
References (recent guidelines and key reviews)
- EORTC/ISCL consensus on SS diagnosis and management, 2021–2024.
- Clinical data for mogamulizumab, ECP combinations, and transplant outcomes, 2021–2024.
- Supportive care in erythrodermic CTCL, 2022–2024.