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A 64 year old female patient with seropositive rheumatoid arthritis (RA) diagnosed in 1997 was referred to our hospital in March 2002, because of high disease activity despite methotrexate (MTX)-sulfasalazine treatment. After exclusion of contraindications infliximab treatment in combination with MTX was started, with good response. At clinical control before the 16th infliximab infusion the patient reported problems with her sinuses. In a computed tomography (CT) scan of that region reactive lymphatic tissue was suspected. Because of the small size (3.5 to 2.8 cm) of the lesion, lymphoma or hypopharynx carcinoma was ruled out. Despite the benign features of the lesion a biopsy was performed, because of the increased risk of malignancy in RA1–3 during disease modifying antirheumatic drug (DMARD) treatment.4,5 Histopathological evaluation and immunohistochemistry led to the diagnosis of an extranodal marginal zone B cell lymphoma of the MALT type. The DMARD treatment was immediately discontinued.
Magnetic resonance imaging (MRI) of the head and neck, CT scans of the thorax and abdomen, ultrasound examination of the abdomen and groin, ileocolonoscopy, and gastroduodenoscopy were unremarkable. Biopsies of the stomach showed Helicobacter pylori infection, which was treated according to the recommendations of Mantzaris et al.6 In bone marrow examinations no evidence of lymphoma infiltration was detected. Signs of Sjögren’s syndrome were not present.
After consultation of oncologists we decided not to start antineoplastic treatment. We agreed on monthly clinical and laboratory controls. The MRI scan of the head and neck carried out 3 and 6 months after primary diagnosis of the lymphoma showed no evidence of a tumour. Biopsy specimens taken again from the region of interest showed no evidence of lymphoma infiltration. We interpreted the available findings as remission of the lymphoma.
Patients with RA are at increased risk of lymphoproliferative disease.1–3 The risk is even higher in patients with increased inflammatory activity.3,7 A proportion of RA associated lymphomas have been attributed to the immunosuppressive effects of DMARDs.4,5
In the case of our patient both risk factors for lymphoma development, high inflammatory activity and DMARD treatment, were present. The patient was treated with MTX for 350 weeks and during that time 4975 mg MTX was ingested. The total dose of infliximab given was 5100 mg. It is unlikely that the marginal zone lymphoma had coexisted for a long time with treatment because of its small size. In addition, reports of the fulminant course of lymphomas after initiating a tumour necrosis factor α antagonist treatment have been published.8
We conclude that in our patient DMARD treatment most probably was responsible for induction of the lymphoma, because complete remission occurred 3 months after stopping the antirheumatic drugs.
There was no difference in steroidal and non-steroidal anti-inflammatory drug use before and after diagnosis of the marginal zone B cell lymphoma, so these drugs are unlikely to have been responsible for the lymphoma remission.
Active RA is a risk factor for lymphoma development. In the follow up of our patient we recorded raised inflammatory activity after discontinuation of DMARD treatment. If disease activity is mainly responsible for the development of the lymphoma, it seems to be unlikely that remission would be achieved during phases of high inflammatory activity.
Discussion continues as to whether a monoclonal expansion of B memory lymphocytes is an inflammatory response to an infectious agent, or a real tumour formation.9 According to published reports the eradication of H pylori infection may induce lymphoma regression.10 However, when all the risk factors in the case of our patient are taken into account, it seems unlikely that antibiotic treatment contributed significantly to remission of the lymphoma.
For clinical routine in cases like ours we recommend that drugs should be withdrawn and the patient monitored closely for evidence of lymphoma regression before initiating specific treatment.
This report was supported by Forschungsverein Innere Medizin Klagenfurt.
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