Normalization of anticardiolipin antibodies following rituximab therapy for marginal zone lymphoma in a patient with Sjögren's syndrome

K. C. Harner, L. W. Jackson and J. J. Drabick

Walter Reed Army Medical Center, Washington, DC, USA

Correspondence to: K. C. Harner, Walter Reed Army Medical Center, Rheumatology Clinic, Ward 77, 6900 Georgia Avenue, NW, Washington, DC 20307, USA. E-mail: kyle.harner{at}na.amedd.army.mil

SIR, Sjögren's syndrome (SS) is associated with the development of lymphoma, most commonly marginal zone lymphoma (MZL), and antiphospholipid antibodies (aPL). While a diagnosis of SS places a patient at 44-fold increased risk of developing lymphoma, the association of SS with aPL is less often described [1, 2]. However, the occurrence of secondary antiphospholipid syndrome (APS) in patients with SS has been reported [3]. Few cases in the literature report the occurrence of both aPL and APS in non-SS patients with various forms of lymphoma [4–8].

Rituximab, a chimeric monoclonal CD20 antibody, has been used successfully to treat non-Hodgkin's lymphoma and several autoimmune disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis, autoimmune thrombocytopenia and autoimmune haemolytic anaemia [9]. In addition, rituximab has recently been shown to improve lymphoma associated with SS, as well as the symptoms of SS itself [10].

We describe a case of normalization of anticardiolipin antibodies (aCL) in a patient with SS and secondary APS treated with rituximab for MZL. We feel that this report is of interest as it may relate to future uses of rituximab to treat APS, in particular the catastrophic APS. The patient is a 46-yr-old female who was diagnosed with SS in 1984. At that time, she had typical sicca symptoms, a positive minor salivary gland biopsy and an antibody profile consistent with the diagnosis (positive ANA, positive SSA/SSB and positive high-titre RF). Initially, symptomatic treatment was successful. In 1995, the patient presented with left cervical lymphadenopathy, leading to a biopsy demonstrating marginal zone lymphoma (MALT). Staging bone marrow biopsy was negative, as were subsequent bone marrow biopsies. A right cervical lymph node excision in 1997 was consistent with MALT.

In 2001, after presenting with acute pleuritic chest pain, the patient underwent evaluation for suspected pulmonary embolus. Imaging revealed a right common iliac deep venous thrombosis, without evidence of pulmonary embolus. Concurrent with the initiation of anticoagulation, an evaluation for a possible hypercoagulable state yielded positive aCL on two occasions. Lupus anticoagulant was negative on both occasions. She has continued on warfarin therapy for secondary APS without recurrent thromboembolic events to date.

In 2002, the patient experienced recurrence of her pulmonary lymphoma by surveillance computed tomography (CT) and positron emission tomography (PET) scans. Upon surgical excision of this lesion, pathology again revealed marginal zone lymphoma. Due to continued recurrence of her lymphoma, rituximab was initiated in 2003 using a standard protocol. In addition to inducing stability of the lymphoma and decreasing her SS symptoms, rituximab normalized the patient's previous high-titre ACL antibodies (Table 1). Follow-up CT and PET scans since administration of rituximab show no recurrence of disease. The patient will undergo a 2-yr maintenance regimen of rituximab at a minimum to continue to treat marginal cell lymphoma and her underlying connective tissue disease.


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TABLE 1. The patient's aCL antibody titres (U/ml) before and after treatment with rituximab in January 2003

 
In our patient, the normalization of aCL was fortuitous and not the reason for initiating rituximab therapy. To our knowledge, this is the first case report of such an association. We realize it is difficult to determine the cause of this patient's deep venous thrombosis, which might have been either due to secondary APS (from underlying SS or lymphoma) or paraneoplastic, although the latter is rare. However, we feel that the high titre of the aCL is significant. In addition, we realize that aPL levels can vary over time, but such a dramatic decrease is probably due to the use of rituximab in this case. We feel that this case illustrates the effectiveness of rituximab in reducing high-titre aCL levels to a normal range. This finding, if validated by other case reports and trials, could have dramatic implications for the use of rituximab in treating and preventing complications due to APS, in particular catastrophic APS. In conclusion, rituximab could be used as primary therapy for this difficult syndrome.

The views expressed in this case report are those of the authors and are not necessarily those of Walter Reed Army Medical Center, the Department of the Army, or the Department of Defense.

The authors have declared no conflicts of interest.

References

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  2. Asherson RA, Fei H, Staub HL, Khamashta MA, Hughes GRV, Fox RI. Antiphospholipid antibodies and HLA associations in primary Sjogren's syndrome. Ann Rheum Dis 1992;51:495–8.[Abstract]
  3. Ingram SB, Goodnight SH Jr, Bennet RM. An unusual syndrome of a devastating noninflammatory vasculopathy associated with anticardiolipin antibodies: report of two cases. Arthritis Rheum 1987;30:1167–72.[ISI][Medline]
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  8. McGuire D, Zeidman A, Mittelman M. Non-Hodgkin's lymphoma presenting with coagulopathy due to anti-phospholipid antibody syndrome. Leuk Lymphoma 1997;26:193–6.[ISI][Medline]
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  10. Somer BG, Tsai DE, Downs L, Weinstein B, Schuster SJ. Improvement in Sjogren's syndrome following therapy with rituximab for marginal zone lymphoma. Arthritis Rheum 2003;49:394–8.
Accepted 15 June 2004





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