Rheumatology 2004; 43: 674-675
Rheumatology Vol. 43 No. 5 (c) British Society for Rheumatology 2004; all rights reserved
Letter to the Editor |
Delayed maculopapular, urticarial rash due to infliximab in two children with systemic onset juvenile idiopathic arthritis
Pediatrics, Ankara University, Medical School, Ankara, Turkey
Correspondence to: E. Tutar. E-mail: tutor{at}dialup.ankara.edu.tr
Sir, The tumour necrosis factor-
(TNF-) blockers (infliximab and etanercept) have been widely used for the treatment of uncontrolled rheumatoid arthritis in adults, but there is little experience with infliximab in children with juvenile idiopathic arthritis (JIA) [1, 2]. Here we describe adverse drug reactions in two children treated with infliximab for systemic onset JIA (s-JIA).
Patient A (girl, 10 yr) and patient B (boy, 16 yr) were diagnosed as having s-JIA at the ages of 3 and 7 yr respectively. Both received combined treatment with non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (standard-dose oral prednisolone and intravenous pulse methyl prednisolone), methotrexate and cyclosporin A. Despite intensive treatment efforts, systemic features and destructive polyarthritis persisted in both patients. The patients also experienced growth retardation and osteoporosis. Because they did not respond to classical drug therapy, we planned to start infliximab infusion (doses of 5 mg/kg at weeks 0, 2 and 6, followed by doses given every 8 weeks). NSAIDs and oral corticosteroids were continued during the initial period of infliximab treatment. After two doses of infliximab infusion, the systemic illness was monitored by clinical and laboratory assessment in both patients; acute-phase reactants decreased remarkably and clinical parameters [visual analogue scale measurement (parental assessment) for global well-being and pain (scale 0–100 mm), Childhood Health Assessment Questionnaire] improved significantly.
The first and second infliximab infusions were tolerated well, except for a transient fever observed in both patients. On the 11th day of the first infusion of infliximab, bilateral severe conjunctival injection was noted in patient A. Two days later, an erythematous diffuse macular, papular and urticarial pruritic rash of the trunk and limbs, some of which showed a central clearing (Fig. 1), occurred and lasted 4 days. At the same time, she suffered from headache, high fever, sleeping disturbance, anorexia and vomiting. Laboratory assessment showed leucocytosis with a shift to the left, and an elevated serum C-reactive protein level. Light microscopic examination of a cutaneous punch biopsy revealed lymphocytic exocytosis in the epidermis, and oedema and perivascular inflammation (predominantly lymphocytes) in the dermis. These findings were considered to demonstrate an exanthematous cutaneous drug reaction. There was no immune deposition detectable by immunofluorescence microscopy.
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After the first dose, bilateral conjunctivitis was also observed in patient B on the third day of therapy and resolved spontaneously at the end of the first week. An aphthous stomatitis, gingivitis, and oral herpes infection developed at the same time and continued until the second infliximab dose in patient B. A maculopapular rash similar to that observed in patient A was noted 18 days after the second infliximab infusion and persisted for about 1 week. Histological examination of these lesions showed necrotic keratinocytes and superficial perivascular mild lymphocytic and histiocytic infiltration in the dermis. We did not demonstrate any immune deposition by immunofluorescence microscopy. Both patients were negative for antinuclear antibody and double-stranded DNA antibody, and had normal complement levels. We did not stop infliximab treatment in either patient. Patient A has received seven and patient B has received six infliximab infusions so far, without significant complications. Treatment with corticosteroids was stopped in both patients after the third infusion of infliximab. They are now in remission, as shown by clinical and laboratory tests. Similar cutaneous eruption have not recurred.
Minor side-effects are commonly reported by most patients who receive infliximab. The most commonly reported side-effects are upper respiratory tract symptoms and mild rash and itching, beginning within 24 h of infusion and usually resolving in a few days without need for treatment [3, 4]. We believe that the delayed appearance of rash in our patients suggests the presence of an immunological preparation period. Although a similar rash may appear with an intercurrent viral infection, clinical and laboratory findings did not suggest a viral infection. The appearance of a rash did also not resemble these children’s previous s-JIA rash. A delayed onset of rash, as seen in our patients, has been reported in adult patients with rheumatoid arthritis as hypersensitivity and/or actual cutaneous vasculitis with infliximab and etanercept [3, 5, 6]. Cutaneous vasculitis has also been reported in a paediatric case with s-JIA due to etanercept [7]. Although we could not demonstrate evidence of vasculitis by light and immunfluorescence microscopy, the histological findings in cutaneous biopsy specimens suggest a hypersensitivity reaction [5]. Therefore, we conclude that a short-lived cutaneous rash may appear 2–3 weeks after the introduction of infliximab treatment as a delayed hypersensitivity reaction in children.
The authors have declared no conflicts of interest.
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