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cyclophosphamide&#44; cyclosporine A and&#44; in recent years&#44; rituximab &#40;anti-&#91;cluster of differentiation&#93; CD20 monoclonal antibody&#41; can be employed with a good response&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a> We report two cases of refractory AIHA secondary to SLE treated with rituximab&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Case no&#46; 1&#58; The patient was a 37-year-old woman who had been diagnosed with SLE 10 years ago&#44; and was being treated with hydroxychloroquine &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; She came to the emergency department with severe weakness&#44; arthralgia and mucocutaneous pallor&#46; Laboratory studies revealed a hemoglobin &#40;Hb&#41; level of 5<span class="elsevierStyleHsp" style=""></span>g&#47;dL and a mean corpuscular volume of 81<span class="elsevierStyleHsp" style=""></span>fL&#44; and thus required a transfusion of packed red cells&#46; We found her total bilirubin &#40;TB&#41; to be 2&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL at the expense of indirect bilirubin&#44; haptoglobin of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; lactate dehydrogenase &#40;LDH&#41; of 856<span class="elsevierStyleHsp" style=""></span>U&#47;L and positivity on direct and indirect Coombs tests&#46; The patient was diagnosed with AIHA and treatment was begun with corticosteroids &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg body weight&#47;day&#41; and azathioprine &#40;50<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; The disease became chronic&#44; with corticosteroid-dependent flares&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Case no&#46; 2&#58; The patient was a 19-year-old woman who had recently been diagnosed with SLE and was being treated with azathioprine &#40;50<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; and hydroxychloroquine &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; She came to the emergency department with a fever of 38&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; deterioration of her general health status&#44; polyarthralgia and weakness&#46; Laboratory studies revealed a Hb level of 7&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; TB of 2&#46;16<span class="elsevierStyleHsp" style=""></span>mg&#47;dL with a predominance of indirect bilirubin and LDH was 678<span class="elsevierStyleHsp" style=""></span>U&#47;L&#46; She was diagnosed with AIHA and was treated with corticosteroids at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg body weight&#47;day&#46; She progressed favorably&#44; but subsequently had further hemolytic crises upon corticosteroid tapering&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In both cases&#44; given the persistence of relapses despite corticosteroid and immunosuppressive therapy&#44; it was proposed to initiate treatment with rituximab at a weekly dose of 375<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> for 4 weeks&#44; and the outcome was favorable and rapid&#46; The treatment maintained Hb levels over 12&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dL after 10 and 12 months&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In the first patient&#44; we administered a second course of rituximab 1 year later&#59; however&#44; the second patient achieved a response that she continues to maintain&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The efficacy of rituximab in autoimmune hematologic disorders is probably due not only to the elimination of the pathogenic autoantibody&#44; but to B-cell depletion as antigen-presenting cells and their conversion to producers of cytokines&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Although the impact of rituximab as the first-line treatment of patients with AIHA is still unknown&#44; it has been found to be effective as second-line therapy in prospective and retrospective studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#8211;8</span></a> with rates of relapse-free survival that range from 64&#37; to 100&#37; at 36 months&#46; Moreover&#44; the rate of response to therapy with a combination of rituximab and corticosteroids is significantly higher than that of corticosteroid monotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Autoimmune hemolytic anemia is a serious pathological condition&#46; Thus&#44; an early diagnosis is important&#44; as is intensive treatment to detain the hemolytic process&#46; In our experience&#44; the use of rituximab resulted in a rapid and durable response that continued over time in two patients of similar characteristics&#46; We consider&#44; in this respect&#44; and according to the literature reviewed&#44; that the initiation of this drug should not be delayed&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7&#44;10</span></a> Given the safety and tolerability of rituximab&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> its use as the second-line of treatment should be recommended&#44; instead of the utilization of immunosuppressive agents that have a greater toxicity or rather than splenectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p></span>"
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Journal Information
Vol. 14. Issue 4.
Pages 248-249 (July - August 2018)
Vol. 14. Issue 4.
Pages 248-249 (July - August 2018)
Letter to the Editor
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Rituximab in Refractory Autoimmune Hemolytic Anemia in Systemic Lupus Erythematosus
Rituximab en la anemia hemolítica autoinmune refractaria en lupus eritematoso sistémico
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María Pavo-Blanco
Corresponding author
mpb.mblanco@gmail.com

Corresponding author.
, Marta Novella-Navarro, Rafael Cáliz-Cáliz, Miguel A. Ferrer-González
Servicio de Reumatología, Complejo Hospitalario Universitario de Granada, Granada, Spain
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Dear Editor,

Autoimmune hemolytic anemia (AIHA) is a common manifestation in systemic lupus erythematosus (SLE), and is often refractory to standard treatment. Corticosteroids constitute the first-line treatment, with a rate of initial response of 70%–85%, although the response is maintained 1 year later in less than 20%.1,2 In cases of refractory AIHA, splenectomy has traditionally been the second-line treatment, with a response rate of 60%–70%, resulting in a considerable increase in the risk of severe infections.2 In cases of refractory disease or in which splenectomy is contraindicated, immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine A and, in recent years, rituximab (anti-[cluster of differentiation] CD20 monoclonal antibody) can be employed with a good response.3,4 We report two cases of refractory AIHA secondary to SLE treated with rituximab.

Case no. 1: The patient was a 37-year-old woman who had been diagnosed with SLE 10 years ago, and was being treated with hydroxychloroquine (200mg/day). She came to the emergency department with severe weakness, arthralgia and mucocutaneous pallor. Laboratory studies revealed a hemoglobin (Hb) level of 5g/dL and a mean corpuscular volume of 81fL, and thus required a transfusion of packed red cells. We found her total bilirubin (TB) to be 2.3mg/dL at the expense of indirect bilirubin, haptoglobin of 1mg/dL, lactate dehydrogenase (LDH) of 856U/L and positivity on direct and indirect Coombs tests. The patient was diagnosed with AIHA and treatment was begun with corticosteroids (1mg/kg body weight/day) and azathioprine (50mg/12h). The disease became chronic, with corticosteroid-dependent flares.

Case no. 2: The patient was a 19-year-old woman who had recently been diagnosed with SLE and was being treated with azathioprine (50mg/day) and hydroxychloroquine (200mg/day). She came to the emergency department with a fever of 38.5°C, deterioration of her general health status, polyarthralgia and weakness. Laboratory studies revealed a Hb level of 7.5g/dL, TB of 2.16mg/dL with a predominance of indirect bilirubin and LDH was 678U/L. She was diagnosed with AIHA and was treated with corticosteroids at a dose of 1mg/kg body weight/day. She progressed favorably, but subsequently had further hemolytic crises upon corticosteroid tapering.

In both cases, given the persistence of relapses despite corticosteroid and immunosuppressive therapy, it was proposed to initiate treatment with rituximab at a weekly dose of 375mg/m2 for 4 weeks, and the outcome was favorable and rapid. The treatment maintained Hb levels over 12.5g/dL after 10 and 12 months, respectively (Fig. 1). In the first patient, we administered a second course of rituximab 1 year later; however, the second patient achieved a response that she continues to maintain.

Fig. 1.

Changes in the hemoglobin levels with rituximab (375mg/m2/weekly for 4 weeks). Stabilization in week 3 of treatment and tapering of corticosteroids to 5mg/day.

(0.13MB).

The efficacy of rituximab in autoimmune hematologic disorders is probably due not only to the elimination of the pathogenic autoantibody, but to B-cell depletion as antigen-presenting cells and their conversion to producers of cytokines.5 Although the impact of rituximab as the first-line treatment of patients with AIHA is still unknown, it has been found to be effective as second-line therapy in prospective and retrospective studies,6–8 with rates of relapse-free survival that range from 64% to 100% at 36 months. Moreover, the rate of response to therapy with a combination of rituximab and corticosteroids is significantly higher than that of corticosteroid monotherapy.8,9

Autoimmune hemolytic anemia is a serious pathological condition. Thus, an early diagnosis is important, as is intensive treatment to detain the hemolytic process. In our experience, the use of rituximab resulted in a rapid and durable response that continued over time in two patients of similar characteristics. We consider, in this respect, and according to the literature reviewed, that the initiation of this drug should not be delayed.6,7,10 Given the safety and tolerability of rituximab,8,9 its use as the second-line of treatment should be recommended, instead of the utilization of immunosuppressive agents that have a greater toxicity or rather than splenectomy.8

References
[1]
D. Dierickx, A. Kentos, A. Delannoy.
The role of rituximab in adults with warm antibody autoimmune hemolytic anaemia.
Blood, 125 (2015), pp. 3223-3229
[2]
M.E. Alfonso, A. Bencomo.
Treatment of autoinmune hemolytic anemias.
Rev Cubana Hematol Inmunol Hemoter, 29 (2013), pp. 327-339
[3]
R. Chaturaka, S. Rajapakse, L. Gooneratne.
Rituximab in the treatment of autoimmune haemolytic anaemia.
Br J Clin Pharmacol, 79 (2014), pp. 709-719
[4]
M. Olfat, E.D. Silverman, D.M. Levy.
Rituximab therapy has a rapid and durable response for refractory cytopenia in childhood-onset systemic lupus erythematosus.
Lupus, 24 (2015), pp. 966-972
[5]
B. Garvey.
Rituximab in the treatment of autoinmune haematological disorders.
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[6]
G. Bussone, E. Ribeiro, A. Decjartres, J.F. Viallard, B. Bonnotte, O. Fain, et al.
Efficacy and safety of rituximab in adults’ warm antibody autoinmune haemolytic anemia: retrospective analysis of 27 cases.
Am J Hematol, 84 (2009), pp. 153-157
[7]
F.J. Penalver, A. Alvarez-Larrazn, J.L. Diez-Marin, L. Gallur, I. Jarque, D. Caballero, et al.
Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoinmune hemolytic anemia.
Ann Hematol, 89 (2010), pp. 1073-1080
[8]
X. Zhang, J. Sun.
Lower dose of rituximab in the treatment of elderly autoinmune hemolytic anemia.
Zhonghua Xue Ye Xue Za Zhi, 35 (2014), pp. 236-238
[Article in Chinese]
[9]
H. Birgens, H. Frederiksen, H.C. Hasselbalch, I.H. Rasmussen, O.J. Nielsen, L. Kjeldsen, et al.
A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia.
Br J Haematol, 163 (2013), pp. 393-399
[10]
N.G. Gottardo, D.L. Baker, F.R. Willis.
Successful induction and maintenance of long-term remission in a child with chronic relapsing autoimmune hemolytic anemia using rituximab.
Pediatd Hematol Oncol, 20 (2003), pp. 557-561

Please cite this article as: Pavo-Blanco M, Novella-Navarro M, Cáliz-Cáliz R, Ferrer-González MA. Rituximab en la anemia hemolítica autoinmune refractaria en lupus eritematoso sistémico. Reumatol Clín. 2018;14:248–249.

Copyright © 2017. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
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