Large paraspinal abscess as a complication of infliximab therapy in Crohn’s disease

Abstract

We report a 36-year-old man who developed a large epidural and paraspinal abscess as a complication of infliximab therapy being used for underlying Crohn’s disease. Cultures of the collection grew methicillin-susceptible Staphylococcus aureus, and treatment consisted of abscess drainage, prolonged intravenous and oral flucloxacillin and temporary withholding of his infliximab. While infection-related complications are well described with infliximab therapy, this is the first description of a large paraspinal abscess with epidural extension.

Background

Tumour necrosis factor-alpha (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of a range of inflammatory diseases. Infliximab is a chimeric monoclonal antibody which binds membrane bound and soluble TNF-α, preventing it from binding to TNF-α receptors and disrupting the immune-mediated inflammatory process.^{1 2} While inhibitors of TNF-α such as infliximab, etanercept and adalimumab are effective treatment of conditions such as inflammatory bowel disease, rheumatoid arthritis and psoriatic arthritis, infection-related complications such as tuberculosis, cytomegalovirus and listeriosis are well described in the literature.³ However, bacterial collections involving the paraspinal space have not been described, and Staphylococcus aureus is not a common causative pathogen in infections related to anti-TNF-α therapy.

Case presentation

A 36-year-old man presented to his local medical officer with 7 days of interscapular pain. This occurred on a background of Crohn’s disease, which had been diagnosed 5 years earlier after several months of diarrhoea and abdominal pains. He was started on azathioprine; however, symptoms failed to improve over 6 months. His therapy was escalated to infliximab, which had been administered every 8 weeks for over 4 years and had adequately controlled his Crohn’s disease.

The patient held a professional job and had secure accommodation. He had a healthy weight, and there was no history of recent corticosteroid use, malnutrition, intravenous drug use or issues with personal hygiene.

The local medical officer had prescribed anti-inflammatory medication, but symptoms progressed with the development of interscapular swelling, loss of appetite and night sweats. He attended the emergency department at another hospital and was noted to have a temperature of 38.1°C. Physical examination revealed a prominent interscapular mass that was firm and tender. Neurological examination was normal, and there were no peripheral stigmata to suggest infective endocarditis.

Investigations

Initial blood tests revealed elevated neutrophil count (11.9×10⁹/L), C-reactive protein level (228 mg/L) and erythrocyte sedimentation level (72 mm/hour). CT was performed and identified a large paraspinal abscess. MRI scan (figure 1) also revealed a large paraspinal collection 10×6×6 cm from C5/6 to T3/4, with extension into the left posterior epidural space at T1/2 to T3/4 and mild narrowing of the central canal, without cord compression.

Figure 1.

T2 sagittal MRI revealing a large paraspinal collection from C5/6 to T3/4, with epidural extension at T1/T2 measuring 5×17×21 mm (see "A" in the image).

Under ultrasound guidance, 50 mL of purulent fluid was aspirated. Aspirate culture was positive for methicillin-susceptible S. aureus (MSSA). Blood cultures were negative, and echocardiography did not identify a vegetation.

Treatment

Broad-spectrum antibiotics were commenced, and the patient transferred to our institution to facilitate surgical drainage. On admission here, when culture results were available, his antibiotics were changed to flucloxacillin (2 g every 6 hours). Surgical drainage and washout of the cervicothoracic paraspinal and epidural abscess were undertaken with debridement of necrotic musculature and T1–3 decompression laminectomies. MSSA was reisolated on tissue culture. Histopathology confirmed inflammatory cell infiltrate in the tissue and superficial bony erosion without evidence of acute osteomyelitis.

Postoperatively, he had periods of asymptomatic hypotension and required paracetamol and oxycodone for analgesia. He was transferred back to his original hospital 11 days after surgery and completed 6 weeks of intravenous flucloxacillin and 6 weeks of oral flucloxacillin.

Outcome and follow-up

The patient made a full recovery and remained clinically well at 6 months.

Discussion

We present the first reported case study of a large continuous paraspinal abscess with epidural extension in a patient on infliximab therapy. The clinical diagnosis of a spinal abscess can be challenging in immunosuppressed patients, in whom common symptoms and signs may be absent or subtle. Our patient presented initially with back pain, followed by progressive interscapular swelling and night sweats. In other case reports of patients on infliximab, chest pain and acute on chronic neck pain have been presenting symptoms of an epidural abscess.^{4 5} Our case highlights that the classic triad of fever, back pain and focal neurological signs may not occur simultaneously, if at all, and the importance of monitoring acute back pain for the evolution of symptoms.

In a meta-analysis of 915 patients, Reihaus et al noted the following underlying risk factors for epidural abscess: diabetes mellitus (15%), intravenous drug use (9%), degenerative spinal disease (6%) and alcoholism (5%).⁶ These findings are mirrored in other systematic reviews.^{7 8} Routes of infection include bacteraemia, direct inoculation via invasive spinal surgery, procedures or trauma and contiguous spread from vertebral osteomyelitis or disciitis.^{6 7} The source of infection in our patient is unclear. There was no history of trauma or spinal or orthopaedic procedures. Contiguous spread of infection from the paraspinal musculature to the epidural space is probable; indeed, in Reihaus et al’s meta-analysis,⁶ 14 out of 854 patients with epidural abscess had coexistent paraspinal abscess. Bacteraemia is confirmed in 60% of epidural abscess cases, and this remains a possibility despite negative blood cultures (only one set was taken prior to initiation of antibiotics).⁹ In addition to immunosuppressive therapy, fistulising Crohn’s disease may be an independent risk factor for epidural abscess, although not present in our patient.^{6 10}

The literature supports a slight to moderate increased rate of infection with TNF-α inhibitors and a likely increased risk of ‘serious’ infection, though studies are inconsistent.^{1 3} In a 2015 systematic review of 106 randomised trials, Singh et al concluded an increased risk of serious infections in rheumatoid arthritis patients on standard-dose (OR 1.31, 95% CI 1.09 to 1.58) or high-dose (OR 1.90, 95% CI 1.50 to 2.39) biological agents (including non-TNF-α inhibitors) but not low-dose biologics.¹¹ Similarly, a 2006 meta-analysis of 5014 patients concluded an increased risk of serious infection in patients with rheumatoid arthritis on TNF-α inhibitors compared with controls (OR 2.0, 95% CI 1.3 to 3.1).¹² In contrast, a recent systematic review of 14 950 participants noted that while the rate of opportunistic infections (OR 1.90, 95% CI 1.21 to 3.01) or any infection (OR 1.19, 95% CI 1.10 to 1.29) were increased in patients with inflammatory bowel disease on biological agents, this was not true of serious infections (OR 0.89, 95% CI 0.71 to 1.12).¹³

The most common causative pathogen for epidural abscess is S. aureus, with an increasing prevalence of methicillin-resistant S. aureus.^6–9 Infliximab has traditionally been associated with reactivation of latent tuberculosis and infections with other mycobacterial species, Listeria, fungi and viruses.2 3 14 15 However, there are increasing case reports of invasive S. aureus infections affecting diverse organs in patients on infliximab.^16–18 Empirical therapy for spinal abscess should be determined by likely causative organisms, patient microbial history and local patterns of resistance.

Learning points.

• Acute back pain in an immunosuppressed patient should always raise suspicion for a paraspinal or epidural abscess.

• Tumour necrosis factor-alpha (TNF-α) inhibitors likely increase the risk of serious bacterial infection, though the literature is inconsistent.

• The clinician should consider Staphylococcus aureus as a causative pathogen in infections related to anti-TNF-α therapy.

• Early recognition and prompt medical and surgical management is vital to preventing permanent neurological disability and death.