Evans syndrome: clinical perspectives, biological insights and treatment modalities

Figures & data

Figure 1 Diagnostic approach for Evans syndrome.

Abbreviations: aCL, anticardiolipin; ALPS, autoimmune lymphoproliferative syndrome; ANA, antinuclear antibodies; anti-CCP, anti-cyclic citrullinated peptide; anti-LC1, anti-liver cytosol antibody; anti-MCV, anti-mutated citrullinated vimetin; anti-Sm, anti-Smith antibody; APS, antiphospholipid syndrome; CVID, common variable immunodeficiency; LA, lupus anticoagulant; LKM-1, liver kidney microsomal type 1 antibodies; PA-IgG, platelet-associated IgG; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SMA, smooth muscle antibody; TSI, thyroid stimulating immunoglobulin; VEGF, vascular endothelial growth factor.

Table 1 Principal mechanisms proposed to explain the pathogenesis of Evans syndrome

Studies	Design	Population	Patients	Mechanism
Besnard et al, 2018^Citation8	Retrospective cohort	Children with ES	18	CTLA-4, LRBA, KRAS, STAT3 gain-of-function mutations are associated with ES secondary to a loss of T-cell homeostasis.
Stepensky et al, 2015^Citation21	Clinical trial	Children with ES	2	TPP2 is an essential molecule for cell survival under stress; deficiency is associated with higher levels of autoantibodies, ABCs, perforins and MHC I, with a consequent immunosenescence; there is an increased risk for viral infections and development of autoimmunity.
Karakantza et al, 2000^Citation23	Short report	Children with ES	1	Increased levels of Th1 cytokines, especially INF-γ, explains the presence of autoreactive B-cells against platelets and erythrocytes, confirmed by the lower levels of IFN-γ after splenectomy.

Abbreviations: ABCs, age-associated B cells; ES, Evans syndrome; INF, interferon; MHC I, major histocompatibility complex I; CTLA-4, cytotoxic T-lymphocyte antigen 4; LRBA, lipopolysaccharide responsive beige-like anchor protein; TTP2, tripeptidyl peptidase 2.

Table 2 Second-line therapeutic options for patients with Evans syndrome

Drug	Dose	Route of administration	Results
Rituximab	N/A^Citation9	N/A	CR: 5; PR: 4; NR: 2
	375 mg/m^2/week/4 doses^Citation98	N/A	Remission: 1/1
	375 mg/m^2/week/3–4 doses^Citation74	N/A	Remission: 13
	375 mg/m^2/week/4 doses^Citation99	N/A	Good response
	375 mg/m^2/week/4 doses^Citation100	N/A	Remission: 1/1
	375 mg/m^2//week/4 doses^Citation101	IV	Remission: 1/1
	375 mg/m^2/week/4 doses^Citation102	IV	Good response: 1/1
	375 mg/m^2/week/4 doses^Citation34	IV	NR: 1
	375 mg/m^2/day/8 doses^Citation103	N/A	NR: 1
	375 mg/m^2/week/3 doses^Citation96	IV	Response: 5/5
	375 mg/m^2/week/4 doses^Citation104	IV	Remission: 1/1
	375 mg/m^2/week^Citation97	IV	Patient 1: NR to AIHA, but CR for ITP; Patient 2: NR; Patient 3: CR for AIHA, NR for ITP; Patient 4: NR to AIHA
	375 mg/m^2/3 weeks/5 doses^Citation105	IV	Good response: 1/1
	375 mg/m^2/week^Citation106	IV	Remission: 1/1
	375 mg/m^2/week/6 weeks^Citation157	IV	Remission: 2/2
	375 mg/m^2/week/4 weeks^Citation69	IV	Response: 1/1
Alemtuzumab	10 mg/day/10 days^Citation134	IV	Response: 2; transient response: 1
Mycophenolate mofetil	650 mg/m^2/b.d.^Citation108	N/A	Response: 14
	50 mg/kg/day^Citation111	N/A	Complete remission: 1/1
	50 mg/kg/day^Citation110	N/A	Sustained remission: 1/1
	500 mg/day, then 1–3 g/day^Citation158	N/A	Response: 10, one with ES
	500 mg/day/b.d., then 1 g/day/b.d.^Citation107	N/A	Response: 4
Cyclosporine	N/A^Citation114	N/A	Relapse
	6 mg/kg/day^Citation115	N/A	Response: 1/1
	N/A^Citation119	N/A	CR: 16/18
	10 mg/kg/day/8 months^Citation116	N/A	Remission: 1/1
	5 mg/kg/day/b.d. for 6 days, then 3 mg/kg/day^Citation118	N/A	PR: 1/1
	5–6 mg/kg/day divided b.d.^Citation120	Oral	Response: 5
	10 mg/kg/day, alternative days^Citation117	N/A	Response
Cyclophosphamide	1,000 mg^Citation129	IV	CR: 6/8
	50 mg/kg/day/4 days^Citation159	N/A	Remission: 1, NR: 1
	500 mg/m^2/4 weeks^Citation130	N/A	PR: 1/1

Abbreviations: AIHA, autoimmune hemolytic anemia; b.d., twice daily; CR, complete response; ES, Evans syndrome; ITP, immune thrombocytopenic purpura; IV, intravenous; N/A, not available; NR, no response; PR, partial response.

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