Pediatric Rheumatology Online Journal → June 2003 → Medical Treatment → Anti-tumor necrosis factor therapy→ Abstract #58
                                                                August 2003 → Newer Treatments → Anti-Tumor Necrosis Factor Therapy → Abstract #58

DISSEMINATED HERPES SIMPLEX (HSV) INFECTION PRECIPITATING MACROPHAGE ACTIVATION SYNDROME (MAS) IN A CHILD WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS (SJIA) UNDERGOING THERAPY WITH INFLIXIMAB

J. M. Skripak,¹ G. L. Rodgers,² C. Martucci,¹ D. P. Goldsmith.¹

¹Section of Rheumatology, St. Christophers Hosp for Children/Drexel University College of Medicine, Philadelphia, PA; ²Section of Infectious Disease, St. Christophers Hosp for Children/Drexel University College of Medicine, Philadelphia, PA

Serious infections have been reported with the use of infliximab; these include bacterial (Listeria monocytogenes, Streptococcus pyogenes), mycobacterial (M. tuberculosis, nontuberculous mycobacteria), fungal (Aspergillus, Candida, Coccidiomycosis, Cryptococcus, Histoplasma and Mucor) viral (varicella zoster) and Pneumocystis carinii.
We describe an 8 year old female with severe, progressive SJIA who developed disseminated herpes simplex virus (HSV) infection leading to MAS while receiving infliximab. The patient had onset of symptoms leading to the diagnosis of SJIA at 3 years of age. Despite aggressive therapy with corticosteroid pulses, methotrexate, cyclosporine, intravenous immunoglobulin G and etanercept, disease progressed. Infliximab was administered (3 mg/kg at weeks 0, 2 and 6, and 5 mg/kg at week 12). Three weeks after the last dose of infliximab she developed sustained fever, oral mucosal lesions and hematemesis. Physical examination revealed numerous ulcerative oral lesions and massive hepatoslenomegaly. HSV-1 was isolated from the oral mucosa and HSV PCR was positive in the cerebrospinal fluid (CSF). Active macrophage phagocytosis of various hematopioetic cells was seen in the CSF and bone marrow. Treatment with parenteral corticosterioids, cyclosporine and acyclovir was initiated. Clinical course was complicated by multiorgan system failure and coagulopathy but ultimately she had a full recovery.
This is the first report of disseminated HSV infection associated with infliximab leading to MAS in a child with SJIA. MAS is a protean disorder of unknown etiology most often seen as a complication of SJIA. Changes in medications and several viruses have been implicated as triggers. Clinicians should be alert to the possibliity of the occurrence of disseminated HSV infection in children with SJIA being treated with infliximab or other TNF blocking agents.