Sezary syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Overview

Sezary syndrome (SS) is one of the most common subtypes of cutaneous T cell lymphoma (CTCL). Sezary syndrome is an erythrodermic cutaneous T-cell lymphoma with a leukemic involvement of malignant T cells with or without lymphnod and visceral organ involvement. SS is closely related to mycosis fungoides (MF), and the two disorders are diagnosed and staged by the same criteria .Cutaneous T cell lymphoma arises from T-cell lymphocytes, which are normally involved in the cell mediated immune response. Sezary Syndrome constitute the broad spectrum of cutaneous T cell lymphoma.

Historical Perspective

  • Sezary syndrome (SS) was first described by Albert Sézary in 1938.[1]
  • The association between cell count of lymphocytes in the peripheral blood with grooved, lobulated (that is, “cerebriform”) nuclei and Sezary syndrome was made in the early to mid-20th century.[2]

Classification

  • The staging of sezazry syndrome is based on the TNMB:[3]
  • Sezary syndrome is defined by T4 erythroderma of body surface area (BSA) more than of 80 percent, Sezary cell is more than 1000 cells/microL in B2 involvement of peripheral blood staged of Sezary syndrome is based on the presence of nodal and/or visceral involvement[4]
Staging for mycosis fungoides and Sezary syndrome
Skin (T)
T1 Limited patches, papules, and/or plaques covering <10% of the skin surface. May further stratify into T1a (patch only) versus T1b (plaque patch)
T2 Patches, papules, or plaques covering 10% of the skin surface. May further stratify into T2a (patch only) versus T2b (plaque patch).
T3 One or more tumours (1-cm diameter)
T4 Confluence of erythema covering 80% body surface area
Node (N)
N0 No clinically abnormal peripheral lymph nodes; biopsy not required
N1 Clinically abnormal lymph nodes; histopathology Dutch grade 1 or NCI LN0-2
N1a Clone negative
N1b Clone posetive
N2 Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3
N2a Clone negatove
N2b Clone posetive
N3 Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3e4 or NCI LN4; clone positive or negative
NX Clinically abnormal peripheral lymph nodes; no histologic confirmation
Visceral (M)
M0 No visceral organ involvement
M1 Visceral involvement (must have pathology confirmation and organ involved should be specified)
Blood (B)
B0 0 Absence of significant blood involvement: 5% of peripheral blood lymphocytes are atypical (Sezary) cells B0a Clone negative B0b Clone positive
B1 Low blood tumour burden: >5% of peripheral blood lymphocytes are atypical (Sezary) cells but does not meet the criteria of B2 B1a Clone negative B1b Clone positive
B2 High blood tumour burden: 1000/mL Sezary cells with positive clone

The staging of Sezary syndrome is based on the clinical stages:[3][5]

clinical stages
Stage T N M B DDS
IA 1 0 0 0/1 98
IB 2 0 0 0/1 89
IIA 1.2 1.2 0 0/1 89
IIB 3 0-2 0 0/1 56
IIIA 4 0-2 0 0 54
IIIB 4 0-2 0 1 48
IVA1 1-4 0-2 0 2 41
IVA2 1-4 3 0 0-2 23
IVB 1-4 0-3 1 0-2 18

Pathophysiology

Microscopic pathology

Causes

Clinical Features

History


Signs

Common signs of Sezary syndrome include:[35]

Skin lesions

The other skin lesion symptoms of Sezary syndrome are:

Other Signs

Some patients with Sezary syndrome have[37][38]

Differentiating Sezary syndrome from other Diseases

Epidemiology and Demographics

  • The prevalence of Sezary syndrome is exact unknown.[45]
  • In 2005 and 2009 the incidence of Sezary syndrome was estimated to be 0/08 and 0/09 cases per 100,000 individuals in the United States.[46][47]

Age

Gender

Race

  • Sezary syndrome usually affects individuals of the whites race.[51]
  • Sezary syndrome is rare disease that tends to affect Whites [51] but in this study African american has more percentage[52]

Risk Factors

Complications and Prognosis

Diagnosis

  1. Erythroderma covering body surface area (BSA) >80%
  2. By PCR or southern blot analysis a clonal TCR rearrangement identified in blood
  3. Sezary cell count >1000 cells/microL or one of the following two criteria :
    1. Increased CD4+ or CD3+ cells with a CD4 to CD8 ≥ 10
    2. Increased CD4+ cells with an abnormal phenotype ( CD4+CD7- ≥40 % or CD4+CD26- ≥30%)

Symptoms

Physical Examination

Laboratory Findings

Laboratory tests for cutaneous T cell lymphoma include:[64]

Treatment

The mainstay of therapy for Sezarey syndrome (SS) is similar to treatment for mycosis fungoides (MF).[67][68][69]

Medical Therapy

Primary treatment
Agent Combination therapy Comment
ECP this therapy is only in some specialized centers.
Retinoids (bexarotene, acitretin, isotretinoin, all-trans retinoic acid) Systemic therapy can be combined such as:
  1. Hyperlipidemia
  2. Central hypothyroidism (bexarotene)
Interferon alpha

Interferon gamma

Systemic therapy can be combined :

Skin directed therapy: Topicals, PUVA

Methotrexate (Low dose) Systemic therapy can be combined:

Skin directed therapy

Side effects:
Histone deacetylase HDAC inhibitors (vorinostat, romidepsin) Systemic therapy can be combined: Side effect:
Secondary treatment
Secondary treatment recomanded after inadequate response, refractory disease or progression despite primary treatment ( Pegylated liposomal doxorubicin, Gemcitabine, Alemtuzumab, Chlorambucil, Fludarabine, Cladribine, Pentostatin, Methotrexate(intermediate dose), Low dose pralatrexate, Brentuximab vedotin, Pembrolizumab)

Prevention

  • There are no primary preventive measures available for [disease name].
  • Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
  • Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
  • Pneumococcal vaccination ld be systematically recommended
  • Prophylaxis with co-trimoxazole and valaciclovir is when the CD4 count is < 0·2 × 109 cells L-1

References

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