Septic abscess in a child with juvenile idiopathic arthritis receiving anti-tumor necrosis factor-alpha.

We read with interest the case report by Kaur and colleagues1 of septic arthritis and abscess formation caused by Actinobacillus urea in a patient with rheumatoid arthritis receiving etanercept and methotrexate (MTX). There are many reports of infection associated with tumor necrosis factorα (TNF-α) blocking agents, including those of the superficial skin2 and abscess3-6. There have been post-market reports of etanercept-associated abscesses in the pediatric population with chronic arthritis7. However, none of these cases have been documented in the literature. This includes not even a single case reported in the open-label extension study8 of etanercept for treatment of juvenile idiopathic arthritis (JIA), now through 4 years of followup9. Recently, we cared for a child who developed a deep abscess while on treatment with etanercept and MTX. An 11-year-old African-American girl was diagnosed with polyarticular JIA 4 months prior to presentation to the emergency department with a fever to 102°F and an 8 × 10 cm area of erythema and tenderness over the left flank. She reported an insect bite to the area occurring the day before. Her current therapy consisted of etanercept 25 mg subcutaneously twice a week (started 2 months before), MTX 25 mg subcutaneously weekly (started 4 months before), prednisone 10 mg orally daily, and naproxen 500 mg orally twice a day. In the emergency department she was given intravenous clindamycin, but within several hours of admission the area of tenderness and erythema spread rapidly. A magnetic resonance scan showed heterogeneous abnormal low signal in the subcutaneous flank in T1-weighted images and heterogeneous high signal in T2 (Figure 1). This is consistent with necrotizing fasciitis, and extended from the inferior liver to the iliac crest, roughly 16 cm in total length. She was taken to surgery, where the area was dissected down to the fascia. A localized area of pus in the soft tissue was debrided and a penrose drain was placed. A biopsy of the fascia showed evidence of inflammation but not necrosis. She remained hospitalized over the next 5 days with continued serosanguinous drainage from the wound, undergoing antibiotic therapy with vancomycin and clindamycin. The abscess culture grew methicillin-resistant Staphylococcus aureus sensitive to clindamycin, vancomycin, and trimethoprim-sulfamethoxazole. She was discharged on a 14-day course of trimethoprim-sulfamethoxazole. Etanercept and MTX were stopped during the phase of active infection. After antibiotic therapy was completed, MTX was restarted and etanercept was changed to adalimumab, 40 mg subcutaneously every 2 weeks. Etanercept appears to be an effective therapy for polyarticular JIA unresponsive to more traditional therapy of intraarticular corticosteroid injections and MTX8,10. However, as noted by Kaur and colleagues, 21% of adverse events attributable to etanercept are infection-related, and physicians must be vigilant in screening for early evidence of infection1. Additionally, Song, et al reported that infliximab, a TNF-α inhibitor not currently approved for treatment of pediatric arthritis, delayed the onset and reduced the incidence and severity of abscess formation induced with S. aureus in a primate model11. Conversely, in the same study, etanercept caused a modest increase in the incidence and severity of abscess formation11. Thus, not all TNF-α inhibitors may share the same risks for infections [e.g., monoclonal antibodies (infliximab and adalimumab) versus soluble TNF-receptor fusion proteins (etanercept)]. Our case of a deep tissue abscess occurring during TNF-α inhibition highlights the importance of close attention to the safety profiles of biologic agents used to treat JIA.