Clinical features

Generalised erythroderma involving ≥ 80% body-surface area, frequently with severe pruritus.
Diffuse alopecia, ectropion, palmoplantar keratoderma, nail dystrophy.
Generalised lymphadenopathy.
Patients are often elderly (median 60–65); slight male predominance.
Constitutional symptoms — weight loss, fatigue, sleep disturbance from intractable pruritus.

Diagnostic criteria (B2 involvement)

Erythroderma (T4) plus blood (B2) involvement. The B2 threshold is a Sézary-cell count ≥ 1000/µL (peripheral smear or flow cytometry).
- Supporting immunophenotypic surrogates (used diagnostically to identify/quantify the clonal population, but not the B2 definition itself): CD4:CD8 ratio ≥ 10; CD4+CD7- cells ≥ 40% of lymphocytes; CD4+CD26- cells ≥ 30% of lymphocytes.
Demonstration of an identical T-cell clone in skin and blood by TCR-γ PCR or high-throughput sequencing.
Patients meeting B2 criteria without erythroderma should be staged as advanced MF with B2 disease, not Sézary syndrome.

Skin histology may be subtle — non-specific perivascular lymphocytic infiltrate; less obvious epidermotropism than classical MF.
Diagnosis often rests on demonstration of the circulating clone with matching skin clone.
Lymph-node biopsy useful where dermatopathic lymphadenopathy is suspected — staging-defining if N3 disease present.

Sézary syndrome is by definition stage IVA1 (B2 N0–2 M0), IVA2 (any T N3 M0) or IVB (any M1).
Baseline workup — full skin/nodal exam, FBC with film, flow cytometry, TCR clonality, LDH, β2-microglobulin, CT NCAP, lymph-node biopsy if N3 suspected, bone-marrow biopsy in selected cases.

First-line UK approach:
- Extracorporeal photopheresis on a 2–4 weekly schedule.
- Combine with low-dose interferon-α and/or oral bexarotene as tolerated.
Second-line / refractory:
- Mogamulizumab — anti-CCR4 antibody, NICE TA754 for previously treated MF / Sézary syndrome.
- Methotrexate, gemcitabine, liposomal doxorubicin.
- Histone deacetylase inhibitors (vorinostat, romidepsin).
- Brentuximab vedotin if CD30+ (TA577).
Allogeneic stem-cell transplantation — reduced-intensity conditioning; only durable cure in younger fit patients with refractory disease.
Supportive care — pruritus (sedating antihistamines, mirtazapine, gabapentin), skin barrier (emollients, occlusive bandaging), skin-infection prophylaxis (Staphylococcus aureus colonisation common), psychosocial support.

Historically median overall survival 2–4 years; outcomes have improved with mogamulizumab and ECP-based regimens.
Adverse features — age, raised LDH, N3 disease, large-cell transformation, refractoriness to ECP.
Follow-up — every 6–8 weeks while on systemic therapy, with monitoring of bloods, flow cytometry and disease symptoms; lifelong skin surveillance.