Delayed multiple injection site reaction in a rheumatoid arthritis patient treated with etanercept
S. Rajakulendran and
C. Deighton
Department of Rheumatology, Derbyshire Royal Infirmary, Derby, UK
Correspondence to: C. Deighton. E-mail: chris.deighton{at}sdah-tr.trent.nhs.uk
SIR, The more common side-effects reported with etanercept are mild transient injection site reactions, upper respiratory tract infections, headaches and rhinitis [1, 2]. We describe a delayed multiple injection site reaction in a patient commenced on etanercept.
A 55-yr-old woman had a 20-yr history of seronegative rheumatoid arthritis (RA). She had been treated unsuccessfully with nine different disease-modifying anti-rheumatic drugs which were stopped due to either lack of efficacy, abnormal blood parameters or intolerance. Her disease remained active so that in March 2004 it was decided to commence her on etanercept therapy (25 mg subcutaneously twice weekly). She appeared to tolerate the first five injections well and her disease activity was reducing. However, on attending the day case unit for routine assessment and her sixth injection she was noted to have developed an erythematous, warm, urticarial itchy rash at all of her previous four rotated injection sites (Fig. 1). Her etanercept injection was omitted and she was prescribed a course of chlorpheniramine. She was reviewed again 4 days later by which time the rash had cleared. Because of the improvement in her RA she has been keen to continue on etanercept treatment. A further similar injection site rash subsequently responded to chlorpheniramine, and she has remained on this drug 4 mg three times daily without further problems.
There have been previous reports of delayed injection site reactions with etanercept and infliximab [36]. Two mechanisms are described for these reactions. The first is an autoimmune process precipitating a cutaneous vasculitis such as discoid lupus, necrotizing vasculitis and leucocytoclastic vasculitis. These rashes tend to be more widespread and not necessarily isolated to the injection sites [35, 7]. The second mechanism describes a T-lymphocyte-mediated hypersensitivity reaction as suggested by an inflammatory infiltrate composed of lymphocytes and eosinophils on biopsy [5, 8]. In one study reported in the dermatology literature, nearly 8% of patients had experienced reactions at previous injection sites (recall injection site reactions) as in this case, although the details are not clear and the reactions were not as widespread as in our patient [8]. The predominant cell type on histology of these sites were CD8+ T lymphocytes. It was hypothesized that these reactions were likely to represent a hypersensitivity reaction in an allergic host. Despite not obtaining a skin biopsy for histology in our patient we postulate that her injection site reaction was due to a similar mechanism, given the localized nature of the rash, and the response to anti-histamines.
In our unit we have a lot of experience with etanercept, but we have had no other multiple recall injection site reactions similar to this patient. We draw this to the attention of our colleagues, and reassure them and their patients that despite the worrying appearance of these recall reactions, they can settle with anti-histamines, and in our patient did not necessitate stopping the etanercept that continues to be helpful for her synovitis.
The authors have declared no conflicts of interest.
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Accepted 20 August 2004