Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor alpha (TNF-alpha), is efficacious in the treatment of rheumatoid arthritis and Crohn's disease. We report in detail an unusual adverse reaction to infliximab therapy, a drug-induced lupus-like clinical syndrome. A 45-year-old woman with steroid-dependent Crohn's colitis, successfully managed with maintenance infliximab infusions and methotrexate, developed a lupus-like syndrome eight months after her initial infusion. This was characterized by inflammatory arthritis and an urticarial and papulosquamous rash and was accompanied by high titers of antinuclear, double-stranded DNA, glomerular-binding, and histone antibodies and by reduced levels of the C4 component of complement. After discontinuance of infliximab infusions and treatment of symptoms with intermittent courses of prednisone, the patient's arthritis progressively improved, with accompanying decrements in autoantibody titers. One year later, she has minimal joint discomfort and no rash or gastrointestinal symptoms despite also discontinuing prednisone and methotrexate. Infliximab therapy may cause a lupus-like syndrome that is reversible upon discontinuing this agent. These findings support recent evidence identifying TNF-alpha as an inhibitor of autoantibody formation.

Enthesitis is a cardinal feature of spondylarthropathy (SpA) (1). One of the most challenging issues in the treatment of SpA concerns refractory heel pain caused by Achilles enthesopathy, retrocalcaneal bursitis, and plantar fasciitis (2). Early reports suggest that the anti-tumor necrosis factor ␣ monoclonal antibody, infliximab, is very efficacious in patients with severe SpA (3,4). We now report our experience with 2 HLA-B27-positive SpA patients who had refractory erosive calcaneal enthesitis without any other articular or axial symptoms, and who experienced significant remission, documented by ultrasonography, following initiation of treatment with infliximab.Both patients received a 3-mg/kg infusion of infliximab at weeks 0, 2, and 6, which was well tolerated. Control examinations were subsequently performed at weeks 10 and 14. At each visit, heel pain was measured on a visual analog scale (VAS), clinical and ultrasound examinations were performed by independent examiners, and the serum level of C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined. Ultrasound examination was performed with real-time high-resolution equipment (AU5 Harmonic; Esaote, Genova, Italy) using a 13-MHz linear array transducer. Inflammatory activity was evaluated using the power Doppler mode at the following settings: medium flow optimum, low wall filter, dynamic range 50 dB, pulse repetition frequency 750 Hz.The first patient, a 21-year-old man, presented with a 10-year history of inflammatory right heel pain and a 3-year history of left heel pain, corresponding with radiographically evident erosions of both calcanei. Prior treatments had included nonsteroidal antiinflammatory drugs (NSAIDs), sulfasalazine (SSZ) for 2 years, multiple local injections of corticosteroids, local radiotherapy, and even local surgery, all of which proved unsuccessful. The patient had stopped working as a baker because of the disabling heel pain. The level of pain on a 100-point VAS was 76 for the right heel and 56 for the left heel. Physical examination at baseline revealed bilateral painful and tender heels at the insertion of the Achilles tendon and plantaris fascia. Magnetic resonance imaging showed bilateral edema and erosions of the entheseal portion of the calcaneus, inflammatory aspects of the Achilles tendon and plantaris fascia. Ultrasound examination revealed bilateral hypoechoic thickening of the Achilles tendon at the entheses, with calcific deposits and bone cortex erosion of the calcaneus ( Figure 1A). Power Doppler sonography showed increased blood flow from the periosteal bone to the entheses of the Achilles tendon and plantaris fascia, predominantly in the left side ( Figure 1A).Partial clinical improvement was noticeable as early as week 2 after the initiation of infliximab treatment (heel pain [for each heel] scored 33 on a 100-point VAS), and complete clinical remission (heel pain scored 0; negative physical findings) was achieved after the second infusion of infliximab (week 6) and was maintained at ...