Rheumatology Advance Access originally published online on November 30, 2005
Rheumatology 2006 45(1):116-117; doi:10.1093/rheumatology/kei227
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LETTER TO THE EDITOR |
Infliximab-induced lupus-like reaction in a patient with psoriatic arthritis
Department of Immunodermatology and 1 Allergology and Immunology Laboratory, Istituto Dermopatico dell’Immacolata, IRCCS, Rome, Italy
Correspondence to: G. Cianchini, Department of Immunodermatology, Istituto Dermopatico dell’Immacolata, IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy. E-mail: g.cianchini{at}idi.it
SIR, Infliximab is a chimeric monoclonal antibody that binds to transmembrane-bound and soluble TNF-
; this drug is currently used in the treatment of several inflammatory diseases, including psoriatic arthritis [1, 2]. Some of the adverse effects linked to its use, although rare, are described as lupus-like syndromes that generally appear in patients with rheumatoid arthritis (RA) [3–5].
We report the case of a 50-yr-old woman with a 20-yr history of psoriasis vulgaris and a subsequent 1-yr history of articular involvement with spondylitis and peripheral asymmetrical oligoarthritis. Previous treatments performed by dermatologists had included cyclosporin, PUVA (psoralen plus ultraviolet light) and methotrexate but they had very little effect on the disease. No significant clinical or laboratory abnormalities were present, except for a positive antinuclear antibody (ANA) test (1:80) with a homogeneous pattern, and no history of clinical features suggestive of lupus was noticed. She was then treated with intravenous infliximab (400 mg at weeks 0, 2, 6 and 14). The patient experienced a rapid improvement of both cutaneous and articular manifestations.
After the third infusion, she developed a high fever and acute thoracic pain due to pleural suffusion. She was given prednisolone 25 mg/day for 7 days and ciprofloxacin 1000 mg/day of for 10 days, which resulted in a temporary improvement. When the patient came to our hospital after the fourth infliximab infusion she had hypophonesis of the right hemithorax. Cardiology was normal but a chest X-ray revealed a right plural effusion. Laboratory tests showed an erythrocyte sedimentation rate (ESR) of 53 mm/h, C-reactive protein (CRP) 11.5 mg/l, fibrinogen 361 mg/dl; platelets 588 000/µl; positive ANA with titre 1/2560 and a homogeneous pattern, single-stranded DNA (ssDNA) 40.6 U/ml and anti-histone antibodies 285 U/ml; anti-extractable nuclear antigens (ENA) and native DNA (nDNA) antibodies were within the normal range. A drug-induced lupus-like syndrome was diagnosed and therapy with 12.5 mg/day prednisolone, 200 mg/day hydroxychloroquine and 10 mg/week methotrexate was started.
Three weeks after discharge, she was readmitted for acute dyspnoea, chest pain, high fever, asthenia and widespread arthralgias consistent with symmetrical polyarticular arthritis. The laboratory tests showed lymphocytosis of 15 540/µl with relative lymphopenia, thrombocytosis (696 000/µl), high ESR (112 mm/h), fibrinogen 809 mg/dl, CRP 192 mg/l, mild proteinuria and haematuria, and an increase in blood sugar levels. A CT chest scan showed a bilateral pleural effusion and an echocardiograph revealed a pericardial effusion. Immunology showed a positive ANA with titre 1/2560 and a homogeneous pattern, and anti-histone antibodies 302 U/ml, but negative anti-centromere, nDNA and ENA antibodies. A bacterial cultural of the pleural effusion, including a check for mycobacteria, was negative and biochemistry showed a clear transudate with mononuclear cells, mainly lymphocytes. Therapy with methylprednisolone 60 mg/day in gradually decreasing doses and methotrexate 15 mg/week was given. Within a few months, a gradual reduction of the clinical symptoms was seen, the ANA titre decreased to 1/160 and anti-histone and anti-ssDNA antibodies disappeared. A year later the patient is being treated with methotrexate 15 mg/week for an acute phase of psoriatic arthropathy.
TNF- is a cytokine that is mainly secreted by monocytes and macrophages. It is known to play a pivotal role in the regulation of inflammatory and immune functions [1]. It also has an important role in the pathogenesis of psoriasis, since it increases the synthesis of proinflammatory cytokines such as IL-1, IL-6 and IL-8, it promotes the migration of leucocytes into the skin by induction of vascular endothelial growth factor (VEGF), it induces adhesion molecule synthesis on keratinocytes and endothelial cells, and it enhances keratinocyte proliferation [3, 6].
Infliximab is used in the treatment of many inflammatory diseases, such as RA, ankylosing spondylitis, Behçet's disease and Crohn's disease [1, 2]. It has also been used successfully to treat several cutaneous diseases. Many studies have shown its efficacy in the treatment of cutaneous and articular psoriasis. The drug quickly improves the skin condition through a reduction in epidermal thickness, the number of epidermal T-cells and the normalization of expression of K16 cytokeratin and intercellular adhesion molecule 1 (ICAM-1) [1].
Infliximab is generally well tolerated, with rare adverse events [1, 2]. The production of autoantibodies is known and well documented. In a study of 62 patients affected by RA, 32 were positive for ANA autoantibodies before treatment and 51 after treatment, whereas seven ANA-negative patients affected by ankylosing spondylitis became positive after therapy [4]. Another report showed the development of ANA, anti-dsDNA (both IgM and IgG) and anti-nucleosome antibodies in a significant number of the 53 patients treated with infliximab for RA [7]. However, the rate of drug-induced lupus is only 0.22% of the patients treated with anti TNF- and two important studies describe a lupus-like syndrome only in 5/2292 treated and 6/1372 cases, respectively [5, 7, 8].
We found no evidence in the literature of lupus-like syndrome induced by anti-TNF- therapy in subjects affected with cutaneous or articular psoriasis.
In conclusion, when considering which psoriatic patients to treat with infliximab, we think it is essential to carry out adequate serum autoimmunity monitoring both before and during therapy and to pay particular attention to any new signs and symptoms that may appear during the course of treatment.
The authors have declared no conflicts of interest.
References
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[Abstract/Free Full Text] - Gottlieb AB, Masud S, Ramamurthi R et al. Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor- monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris. J Am Acad Dermatol 2003;48:68–75.[CrossRef][Web of Science][Medline]
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[Abstract/Free Full Text] - Eriksson C, Engstrand S, Sundqvist KG et al. Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF. Ann Rheum Dis 2005;64:403–7.
[Abstract/Free Full Text] - De Rycke L, Kruithof E, Van Damme N et al. Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy. Arthritis Rheum 2003;48:1015–23.[CrossRef][Web of Science][Medline]
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