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The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases

Marc Michel, Valérie Chanet, Agnès Dechartres, Anne-Sophie Morin, Jean-Charles Piette, Lorenzo Cirasino, Giovanni Emilia, Francesco Zaja, Marco Ruggeri, Emmanuel Andrès, Philippe Bierling, Bertrand Godeau and Francesco Rodeghiero

Article Figures & Data

Figures

Tables

  • Table 1

    Main characteristics of the 68 patients

    CharacteristicsValue
    Sex ratio (females/males)41 (60%)/27
    Mean age at ITP/AIHA onset55 ± 33 y
    Mean (median and range) platelet level (×109/L) at ITP onset and/mean lowest level during follow-up31 (median 12.5: 2 to 100)/18 ± 15
    Mean Hb level (g/dL) at AIHA onset and/mean lowest level during follow-up7.6 ± 1.9/ 6.3 ± 1.2
    DAT pattern
        IgG43%
        IgG + C3d53%
        Negative4%*
    No. of patients (%) who got a transfusion of packed red cell units for AIHA and/mean no. of units per patientN = 32 (47%)/3.7
    No. of patients (%) with ITP-related bleeding symptomsN = 44 (64%)
    No. with a life-threatening hemorrhageN = 3 (4.4%)
    • DAT indicates direct antiglobulin test.

    • * The 3 patients with a negative DAT had a simultaneous thrombocytopenia with a normal marrow and neither features of TTP on the smear nor any other cause of hemolytic anemia.

  • Table 2

    Secondary cases of Evans syndrome, n = 34

    Secondary casesn
    Autoimmune diseases
        Systemic lupus erythematosus7
        “Incomplete” lupus3
        Primary antiphospholipid syndrome2
        Sjögren syndrome2
    Immunodeficiencies
        Common variable immunodeficiency4
        IgA deficiency2
    Lymphomas
        B-cell non-Hodgkin malignant lymphoma2
        Chronic lymphocytic leukemia3
        T-cell non-Hodgkin lymphoma1
    Miscellaneous
        Chronic myelomonocytic leukemia1
        Unclassified lymphoproliferative disorder*3
        MGUS1
        Hepatitis C1
        Congenital asplenia1
        Idiopathic CD4 lymphocytopenia1
    • MGUS indicates monoclonal gammopathy of unknown significance.

    • * Lymphadenopathy, splenomegaly + polyclonal hypergammaglobulinemia (n = 3) with an excess of large granular lymphocytes in 1 case. No features suggesting an ALPS (no excess of CD3+ C α/β+ CD4/CD8 T cells in peripheral blood, no Fas, Fas-L, or caspase 8 genes mutations) has been found.

  • Table 3

    Comparisons of the main characteristics of primary and secondary cases

    Primary ES, n = 34Secondary ES, n = 34P
    Mean age, y62 ± 21.553.5 ± 17.07
    Mean age at diagnosis, y57 ± 2348 ± 19.08
    Sex ratio.4
        Females19 (56%)22 (65%)
        Males15 (44%)12 (35%)
    Occurrence of ITP and AIHA.3
        Simultaneously23 (68%)19 (56%)
        Sequentially11 (32%)15 (44%)
    Mean lowest Hb level, g/dL6.9 ± 1.76.1 ± 2.0.07
    Median lowest platelet level (×109/L)8 (1-100)6 (1-90).5
    Need for transfusion18 (53%)15 (44%).5
    Splenectomy11 (32%)8 (24%).5
    Initial response8 (72%)7 (87%).6
    Deaths9 (26%)7 (20.5%).4
  • Table 4

    Causes of deaths, n = 16

    Causes of deathn
    Infection7
        Septic shock (n = 6) due to Staphylococcus aureus (1), Pseudomonas aeruginosa (1),* unknown bacteria (4); one patient with a prior history of stroke had a fatal aspiration pneumonia
    Cancer3
        Site of cancer: uterus (1), pancreas (1), esophagus (1)
    Cardiovascular3
        Stroke (2), myocardial infarction (1)
    Myelodysplastic syndrome (RAEB)1
    B-cell non-Hodgkin lymphoma1
    Unknown1
    • RAEB indicates refractory anemia with excess of blasts.

    • * A concomitant hemorrhagic stroke was suspected at time of death.

    • Two of these patients had undergone a splenectomy 3 weeks and 2 years prior to death, respectively.

  • Table 5

    Proposals for a minimal work-up in adults with a newly diagnosed ES

    Proposals
    • Blood smear

    • Serum protein electrophoresis and serum immunoelectrophoresis (immunofixation)

    • Measurement of serum immunoglobulin concentrations

    • Immunophenotyping of circulating B lymphocytes

    • Antinuclear ± anti-dsDNA antibodies

    • Anticardiolipid antibodies and lupus anticoagulant assay*

    • HIV and HCV tests, HBV test

    • CT scan of the chest, abdomen, and pelvis

    • Bone marrow biopsy

    • HCV indicates hepatitis C virus; and HBV, hepatitis B virus.

    • * To be considered especially in patients with a history of venous and/or arterial thrombosis and/or in women with recurrent pregnancy loss.

    • To prevent viral reactivation in HBV carriers prior to corticosteroid therapy and especially if rituximab is considered.

    • To be considered in patients with features suggesting a lymphoproliferative disorder (monoclonal gammopathy).