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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 1  |  Page : 109-112
Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus

Department of Medicine, Division of Nephrology and Division of Hematology/Oncology, College of Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia

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Date of Web Publication8-Jan-2010


Thrombotic thrombocytopenic purpura (TTP) is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secon­dary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythe­matosus (SLE) and may be refractory to treatment with plasma exchange, requiring immuno­suppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued re­mission after eight months of follow-up. Rituximab appears to be an effective treatment in re­fractory cases of TTP associated with SLE.

How to cite this article:
Niaz FA, Aleem A. Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus. Saudi J Kidney Dis Transpl 2010;21:109-12

How to cite this URL:
Niaz FA, Aleem A. Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2022 Nov 28];21:109-12. Available from: https://www.sjkdt.org/text.asp?2010/21/1/109/58783

   Introduction Top

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder first described in 1924 by Moschowitz. [1] The majority of cases of TTP are idiopathic without an identifiable cause or associated illness. TTP may occur in asso­ciation with various connective tissue diseases, but has rarely been associated with SLE. [2],[3] In most of the patients, SLE is usually diagnosed earlier and TTP develops, later but both can present simultaneously, or the TTP may de­velop with an exacerbation of SLE causing difficulty and delay in TTP diagnosis because of the overlapping features of these two dis­orders. [2],[4]

TTP is a serious disorder with high mortality if not treated. [5]

There is still a significant mortality with the current treatment strategies, and there is a need to explore new ones for patients who are re­fractory to the conventional treatment. [6],[7] More­over, TTP associated with SLE is thought to be more resistant to plasma exchange, and ear­ly consideration to immunosuppressive thera­py has been recommended. [8],[9] Rituximab is an anti-CD20 antibody, which has demonstrated effectiveness in many autoimmune disorders. [10]

Here we describe a patient who was diag­nosed to have TTP and SLE simultaneously and was refractory to plasma exchange but showed a good response to rituximab.

   Case Report Top

A 34-year-old Saudi woman presented to the emergency department at our institution during November, 2007 with one week history of fe­ver and skin rashes all over the legs. A day prior to the admission, she suffered from an episode of generalized tonic-clonic convulsions followed by confusion and agitation. Her past medical history was unremarkable, but her sister was diagnosed to have SLE few years earlier.

On examination, the patient had normal vital signs, but revealed multiple ecchymotic patches on her both lower limbs. She was confused but there were no signs of meningeal irritation or focal neurological deficit. The rest of her exa­mination was unremarkable. The laboratory in­vestigations revealed the presence of anemia (hemoglobin (Hb) 5.9 g/dL), and severe throm­bocytopenia (platelets count 9 Χ 10 9 /L). The coa­gulation profile was normal. The reticulocyte count was elevated to 12.4%. Liver function tests indicated total and indirect hyperbiliru­binemia (total bilirubin: 50 ΅mol/L, indirect bilirubin: 30 ΅mol/L). Lactate dehydrogenase (LDH) was elevated at 1206 U/L (Normal: 100­190). Peripheral blood smear revealed poly­chromasia and a significant number of schisto­cytes (fragmented red cells). A direct and in­direct Coomb's tests were negative. The renal function tests were normal and urinalysis re­vealed proteinuria (0.83 g/day on 24-hour urine collection).

A computerized tomography (CT) scan of brain was normal. Serologic tests showed ele­vated ANA of 1:5120 and low C3 of 0.569 g/L (normal range 0.7-1.7), while C4, anti-dsDNA, Hepatitis B and C, and HIV were negative. All appropriate cultures were negative. On the ba­sis of these findings, the patient was diagnosed to have thrombotic thrombocytopenic purpura along with SLE.

She was started on daily plasma exchange and received methylprednisolone 500 mg daily for 3 days followed by 60 mg (1 mg/kg) daily. She also received anticonvulsive therapy.

Her platelet count increased to 30 Χ 10 9 /L on the 5th day of treatment but dropped again to 12 Χ 10 9 /L the next day. There was no im­provement till day 11. In view of the refractory disease, immunosuppressive therapy was con­sidered and rituximab was started at a dose of 375 mg/m 2 weekly. Rituximab was tolerated well with no adverse events and the platelet count started to improve after three days of the first dose along with improvement in other parameters such as the reticulocyte count and LDH. Frequency of plasma exchange was re­duced and then discontinued. Patient's labora­tory parameters over the period of time are shown in [Table 1]. Platelet and LDH response to treatment in relation to time are shown in [Figure 1]. The patient received 3 weekly doses of rituximab and the fourth planned dose was not given because of an excellent response. She was also started on hydroxychloroquine and corticosteroids, which were tapered slowly over the next few months. ADAMTS-13 acti­vity could not be tested initially because of non-availability; however, a sample tested few weeks later showed normal activity (> 70%). the patient remained well 8 months post the­rapy with normal laboratory parameters.

   Discussion Top

TTP is a life-threatening disease with high mortality if not treated. [5] Treatment modalities, such as the plasma exchange, have decreased the mortality rate significantly from 90% to less than 20%. [6] For acute TTP, daily plasma ex­change remains the initial treatment of choice in combination with corticosteroids. [6] Patients who do not respond well to this treatment require other modalities of treatment, usually an immunosuppressive therapy. TTP associated with SLE is rare but possibly under-diagnosed disease because of the overlapping features of both entities. [2] TTP secondary to SLE has been reported to be resistant to plasma exchange, and early cytotoxic therapy with cyclophospha­mide has been recommended. [8],[9]

Rituximab is a chimeric, monoclonal anti­CD20 antibody, which specifically depletes B cells. It has demonstrated effectiveness in va­rious autoimmune hematological disorders in­cluding idiopathic TTP. [10] Treatment of refrac­tory or relapsing TTP with Rituximab has been effective with lasting remissions. [11],[12] In a study by Scully et al, all 25 patients with idiopathic TTP attained complete clinical and laboratory remission in a median of 11 days after initia­ting rituximab. [13] There have been occasional reports of successful use of rituximab in re­fractory cases of SLE associated with TTP. [14],[15] In our patient, TTP and SLE were diagnosed simultaneously during the same admission. She was initially treated with daily plasma ex­changes along with high dose corticosteroids without a good response. However, the patient responded successfully to weekly rituximab with clinical and laboratory improvement with­in few days after the first dose. Rituximab was chosen in this patient because of the recent encouraging reports of its effectiveness in this disorder and lesser potential toxicity when compared to cyclophosphamide. Because of the rarity of this disorder, comparative trials of rituximab with cyclophosphamide may not be possible. Because of this reason, case reports of rituximab efficacy as well as its failure, should be encouraged to define the role of this therapy in the management of SLE associated TTP cases, refractory to plasma exchange.

TTP is characterized by microthrombi in various organ systems due to presence of ab­normally large Von Willibrand factor (vWF) multimers in the plasma. ADAMTS-13 is a metalloproteinase, which cleaves large vWF multimers into smaller, inactive monomers. [16] Reduced activity of ADAMTS-13 is associated with many disorders but markedly reduced activity (< 10%) is specific for TTP.[17] ADAMTS­13 activity levels are not only helpful in initial diagnosis of TTP, but also useful in moni­toring therapy, as it rises to higher levels in patients who achieve remission. In our patient, ADAMTS-13 activity could not be measured initially. However, a sample tested few weeks after rituximab therapy and clinical improvement, showed normal (> 70%) activity of ADAMTS­13 consistent with clinical remission and a good response to rituximab therapy. The pa­tient remains in remission after eight months of follow-up.

In conclusion, rituximab appears to be an effective treatment modality for refractory cases of TTP associated with SLE, and we recommend that the use of rituximab should be considered in this setting.

   References Top

1.Moschcowitz E. Hyaline thrombosis of terminal arterioles and capillaries: A hitherto undescribed disease. Proc N Y Pathol Soc 1924;24:21-4.  Back to cited text no. 1      
2.Aleem A, Al-Sugair S. Thrombotic thrombo­cytopenic purpura associated with systemic lupus erythematosus. Acta Haematol 2006;115 (1-2):68-73.  Back to cited text no. 2      
3.Caramaschi P, Riccetti MM, Pasini AF, Savarin T, Biasi D, Todeschini G. Systemic lupus ery­thematosus and thrombotic thrombocytopenic purpura. Report of three cases and review of literature. Lupus 1998;7:37-41.  Back to cited text no. 3      
4.Dold S, Singh R, Sarwar H, Menon Y, Candia L, Espinoza LR. Frequency of microangiopathic hemolytic anemia in patients with SLE exacer­bation: distinction from TTP, prognosis, and outcome. Arthritis Rheum 2005;53:982-5.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Amorosi EL, Ultmann JE. Thrombotic thrombo­cytopenic purpura: Report of 16 cases and re­view of the literature. Medicine 1996;45:139-59.  Back to cited text no. 5      
6.Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic throm­bocytopenic purpura: Canadian Aphresis Study group. N Eng J Med 1991;325:393-7.  Back to cited text no. 6      
7.Torok TJ, Holman RC, Chorba TL. Increasing mortality from thrombotic thrombocytopenic purpura in the United States-analysis of nation­nal mortality data, 1968-1991. Am J Hematol 1995;50:84-90.  Back to cited text no. 7      
8.Vasoo S, Thumboo J, Fong KY. Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: Disease activity and the use of cytotoxic drugs. Lupus 2002;11:443-50.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Perez-Sanchez I, Anguita J, Pintado T. Use of cyclophosphamide in the treatment of throm­botic thrombocytopenic purpura complicating systemic lupus erythematosus: Report of two cases. Ann Hematol 1999;78:285-7.  Back to cited text no. 9      
10.Franchini M, Veneri D, Lippi G, Stenner R. The efficacy of rituximab in the treatment of inhi­bitor-associated hemostatic disorders. Thromb Haemost 2006;96(2):119-25.  Back to cited text no. 10      
11.Fakhouri F, Vernant JP,Veyradier A, et al. Effi­ciency of curative and prophylactic treatment with rituximab in ADAMTS 13-deficient throm­botic thrombocytopenic purpura: A study of 11 cases. Blood 2005;106:1932-7.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Ahmad A, Aggarwal A, Sharma D, et al. Ritu­ximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). Am J Hematol 2004;77:171-6.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Scully M, Cohen H, Cavenagh J, et al. Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura following rituximab is associated with a reduction in IgG antibodies to ADAMTS-13. Br J Haematol 2007;136:451­-61.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]  
14.Niewold TB, Alpert D, Scanzello CR, Paget SA. Rituximab treatment of thrombotic thrombo­cytopenic purpura in the setting of connective tissue disease. J Rheumatol 2006;33(6):1194-6.  Back to cited text no. 14      
15.Limal N, Cacoub P, Sene D, Giuchard I, Piette JC. Rituximab for the treatment of thrombotic thrombocytopenic purpura in systemic lupus erythematosus. Lupus 2008;17:69-71.  Back to cited text no. 15      
16.Levy GG, Motto DG, Ginsburg G. ADAMTS 13 turns 3. Blood 2005;106:11-7.  Back to cited text no. 16      
17.Bianchi V, Robles R, Alberio L, Furlan M, Lammle B. von Willibrand factor-cleaving pro­tease (ADAMTS 13) in thrombocytopenic dis­orders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood 2002;100:710-3.  Back to cited text no. 17      

Correspondence Address:
Faraz Azim Niaz
Department of Medicine, College of Medicine and King Khalid University Hospital,P.O. Box 7805, Riyadh 11472
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 20061703

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  [Figure 1]

  [Table 1]

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