Rheumatology Advance Access originally published online on November 30, 2005
Rheumatology 2006 45(1):114-116; doi:10.1093/rheumatology/kei220
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LETTER TO THE EDITOR |
Drug-induced systemic lupus erythematosus in ankylosing spondylitis associated with infliximab
Arthritis Unit, Department of Rheumatology, Hospital del Mar i Hospital de l’Esperança, Passeig Maritim 25-29, 08003 Barcelona, Spain
Correspondence to: C. Pérez-García. E-mail: 92283{at}imas.imim.es
SIR, Infliximab therapy for the treatment of rheumatoid arthritis and Crohn disease has been associated with the development of polyarthritis, fever, induction of autoantibodies [antinuclear antibodies (ANA) and anti-double-stranded DNA (ds-DNA)] and dermatological events that are all compatible with systemic lupus erythematosus (SLE) [1, 2]. These symptoms have been attributed to the increasing levels of ANA induced during therapy with anti-tumour necrosis factor 
[3]. The induction of autoantibodies in the treatment of ankylosing spondylitis with infliximab has also been described, but to our knowledge it has never been associated previously with induction of a lupus-like syndrome [4, 5].
Criteria for the diagnoses of drug-induced SLE are not well established, but it is widely accepted that there is a temporal relationship between the treatment and the symptoms. We describe the first case reported in the literature of drug-induced SLE in a patient with refractory ankylosing spondylitis, without previous peripheral joint manifestation, treated with infliximab.
A 65-yr-old woman diagnosed with ankylosing spondylitis according to the modified New York criteria [6], a clinical course of more than 15 yr, positivity to HLA-B27 and recurrent episodes of uveitis was referred to the out-patient arthritis unit of a university hospital. Previous treatment with high doses of NSAIDs plus 2 g/day of sulphasalazine for 3 yr failed to control the symptoms. When sulphasalazine was changed to 15 mg methotrexate weekly for 1 yr there was slight improvement, but this treatment was finally stopped due to intolerance. The patient complained of inflammatory low back pain, the Bath Ankylosing Spondylitis Functional Index (BASFI) was 65/100, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 51/100, and spinal mobility measures were as follows: Schöber test 2 cm; chest expansion 2 cm; and occiput–wall 10 cm. Peripheral joint manifestations had been never been present during the 15 yr of disease evolution. After the initial evaluation, we decided to give intravenous infusions of infliximab at 3 mg/kg at weeks 0, 2, 6 and then every 8 weeks. After the first infusion of infliximab the patient was in good clinical condition, with a pronounced decrease in biochemical and clinical parameters (Table 1). According to the Assessment in Ankylosing Spondylitis Response Criteria (ASAS criteria), in the sixth week of treatment with infliximab, the patient presented a reduction of 33.9% in BASFI, 68.8% in BASDAI, 57.3% in visual analogues scale (VAS) for pain and 52.5% in C-reactive protein (CRP). Forty-eight hours after the fifth infusion, the patient was hospitalized with general malaise, fever, myalgias, acute polyarthritis and morning stiffness of more of 1 h. Skin lesions were not present. Serological studies showed ANA 1/5120, anti-dsDNA 38.7 (normal value 40), negative anti-histone antibodies, CRP 8.8 mg/dl (normal value <0.8 mg/dl), erythrocyte sedimentation rate 38 mm in the first hour and lymphopenia. Drug-induced SLE associated with infliximab was diagnosed and treatment with corticosteroids was introduced, with resolution of clinical and biochemical data during the following 2 weeks.
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Drug-induced SLE is a well-known entity, accounting for 5–10% of all lupus syndromes. Infliximab therapy has been associated with a lupus-like syndrome in patients with rheumatoid arthritis and Crohn disease, but never previously in a patient with ankylosing spondylitis. Forty-eight hours after the fifth infliximab treatment, the patient presented with polyarthritis, positivity to ANA and lymphopenia. Although there were no dermatological events and no positivity for anti-DNA or anti-histone antibodies, the obvious temporal relationship suggested the diagnosis of drug-induced syndrome. This is, to our knowledge, the first case described in the literature of infliximab drug-induced SLE in a patient with ankylosing spondylitis.
Several mechanisms have been suggested to explain infliximab-induced lupus. One hypothesis has proposed an increase in apoptotic particles and antigens from apoptotic cells [7]. D’Auria et al. [7], in a recent study, have shown that rheumatoid arthritis patients receiving infliximab therapy have a 24-h increase in plasma nucleosomes, in comparison with undetectable levels before the infliximab infusion. This could explain the increased production of antibodies that is present in SLE [8]. Another hypothesis proposes that the suppression of the T-helper type 1 response by TNF blockers could favour a T-helper type 2 response leading to SLE. Prospective studies in humans are necessary to confirm these data [9]. Another hypothesis is that there is an increase in bacterial infections, with stimulation and activation of B-lymphocyte and autoantibody production [10].
In conclusion, drug-induced SLE is an entity associated with infliximab treatment and we found it in a patient with ankylosing spondylitis.
The authors have declared no conflicts of interest.
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