ReviewManagement of immune cytopenias in patients with systemic lupus erythematosus — Old and new
Introduction
Hematological involvement is common in SLE and no specific treatment is necessary in mild asymptomatic cases but close monitoring of cytopenia is warranted in most patients. Any significant changes in previous stable cell lineage parameters are considered to be an indication of SLE flare, and will need evaluation and close monitoring. This evaluation should include a detailed medical history for possible drug-induced myelosuppression, and in addition to stopping all medications which interfere with bone marrow function. Symptomatic treatment including transfusion therapy is required in cases with more severe hematological abnormalities. For the past 50 years, no new medication has been approved by FDA for SLE. Corticosteroids are considered the first line of treatment in severe cases for decades, and are effective in about 80% of SLE patients with hematological abnormalities. However, significant number of SLE subsets is resistant to conventional therapy and has high mortality and morbidity rates. There are second-line drugs such as immunomodulators and immunosuppressors for corticosteroid-resistant cases, but there is no randomized controlled clinical trial for most of these drugs and their use is anecdotal. Majority of these drugs are nonselective and have substantial toxicity. Moreover, there is no general agreement on definition of flare, response, and resistance and it is hard to compare the response rate of different drugs. More effective and less toxic drugs without any overt adverse effect still remain to be discovered [1], [2]. SLE is the most common cause (38–61%) of ICU admission among all autoimmune disorders and respiratory system is the most common involved organ [3]. In the next few paragraphs we will discuss the different hematologic manifestations of SLE and their treatments.
Section snippets
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AIHA) with or without thrombocytopenia occurs in about 10% of SLE patients and is a common and serious complication in these cases [4], [5], [6], [7]. The warm type AIHA, mediated by IgG antibodies reacting in body temperature is the predominant type in patients with SLE while cold agglutinin AIHA is mediated by IgM complement-fixing antibody, which reacts at 4 °C. Patients with overt hemolysis present with anemia, elevated reticulocyte count, low haptoglobin,
Transfusion therapy in AIHA
Autoantibodies can potentially mask alloantibodies, and make it difficult to find the appropriate red blood cell by compatibility testing. However, sometimes clinicians face patients with progressive or severe symptomatic AIHA and reticulocytopenia that transfusion therapy is necessary and can be life-saving. Importantly transfusion should not be delayed in such situations. Most alloantibodies are directed against the blood group systems of Rh, Kell, Kidd, and Duffy. Occasionally, diluting the
Other types of anemia
Anemia of chronic disease is a frequent cause of anemia in patients with SLE. The pathogenesis is usually secondary to suppression of erythropoiesis by chronic inflammation [6]. Anemia is usually normochromic normocytic with a low reticulocyte count, elevated ferritin and low iron levels, and bone marrow iron is usually adequate. The major mediator of anemia of chronic disease is hepcidin which usually inhibits iron release from macrophages and absorption of iron from intestine, leading to
Leukopenia
Leukopenia is common in SLE and usually is secondary to lymphopenia, neutropenia or combination of both. Eosinopenia and basophilopenia are rare and have lesser clinical significance. Lymphopenia is common and T cell lymphopenia is the most common type of lymphopenias, and absolute lymphopenia correlates with SLE activity and high DNA antibody titers. Lymphopenia per se can predispose to autoimmunity and can also be a consequence of disease activity in the setting of active SLE. Concomitant
Thrombocytopenia
Thrombocytopenia is a common and important manifestation of SLE which has direct relation with its morbidity and mortality. It is mild to moderate most of the time and does not need any specific treatment. However, severe thrombocytopenia occurs in the context of active disease. There are growing evidences that show presence of at least two types of autoantibodies, anti GPIIb/IIIa, and anti thrombopoietin receptor (TPOR) antibodies are the major pathophysiologic mechanisms of thrombocytopenia
Treatment of TTP in SLE patients
Thrombotic thrombocytopenic purpura is a life threatening thrombotic microangiopathy (TMA) that needs high index of suspicion in SLE. TTP can be divided to primary or idiopathic and secondary to an underlying disorder. Severe ADAMTS13 deficiency or presence of its inhibitor is a manifestation of acute idiopathic TTP, relapses are frequent, and plasmapheresis is the standard of treatment. In a large study of patients with connective tissue disorders and TMA the percentage of patients with TMA
Splenectomy in SLE
Splenectomy is an invasive therapeutic modality and a frequent procedure for hematological manifestations of SLE but still the role of splenectomy in SLE associated hemocytopenia is not clear, and even some authors believe it is harmful. In one study, 30 unselected SLE patients with thrombocytopenic purpura and/or AIHA divided to two 15 groups of splenectomy and non-splenectomy and the result in a 19 months follow up for both groups were the same. However, cutaneous vasculitis, infections, and
Take-home messages
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Anemia of chronic disorder is the most common type of anemia in SLE but autoimmune hemolytic anemia with high reticulocyte count is a SLE diagnostic criteria. Glucocorticoids are the main treatment of AIHA and about 96% of patients have initial response to glucocorticoids but rituximab, cyclosporine, IVIg, and cyclophosphamide have successfully been used in selective cases.
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Transfusion may be problematic in AIHA, and even life threatening. Transfusion should be avoided and only be done
Disclosure
All authors do not have any conflict of interest to disclose.
Acknowledgment
The authors wish to thank Kathleen Kruger for her technical assistance.
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