Life threatening intra‐abdominal sepsis in patients on anti‐TNF‐α therapy

Tumour necrosis factor α (TNF‐α) blocking drugs are used in the treatment of a number of inflammatory conditions. It is likely that the use of these drugs will increase. There have been reports of serious infections with these drugs.¹,²,³ Doctors need to be aware of the potential for sepsis, especially as they are increasingly likely to encounter patients on anti‐TNF drugs. We present two cases of life threatening intra‐abdominal sepsis in patients with rheumatological conditions receiving anti‐TNF drugs.

Case 1

A 60 year old male with psoriatic arthritis resistant to treatment had benefited from etanercept for six months. In rheumatology outpatients he complained of a two week history of abdominal pain. On examination he was tender in the left upper quadrant with a palpable mass. A contrast enhanced computed tomography (CT) scan demonstrated a large multiloculated splenic abscess with subcapsular extension (fig 1). Blood cultures grew Staphylococcus aureus. Conservative treatment with high dose intravenous antibiotics, initially with cefuroxime, metronidazole, and gentamicin on microbiological advice, had no effect. The patient became increasingly septic and after one week of conservative therapy he proceeded to laparotomy and splenectomy (fig 2). Postoperatively he developed sepsis requiring ITU admission and high dose inotropic support for five days. Histopathology of the spleen showed multiple splenic abscesses that grew Staphylococcus aureus. The patient made a full recovery. He has received no further etanercept and has no evidence of a flare up of his arthritis six months postoperatively. He was given prophylactic low dose penicillin and anti‐pneumococcal vaccination.

Figure 1 Computed tomography. Expansile predominantly cystic mass located within an area of hypodensity in the posterior pole of the spleen.

Figure 2 Surgical specimen consisting of the spleen with an abscess on the posterior aspect.

Case 2

A 40 year old female presented via A&E with a three day history of abdominal pain and rigors. She had been treated with infliximab for six weeks for severe rheumatoid arthritis resistant to other therapies. On examination she had a pyrexia of 39.2°C with right upper quadrant tenderness. She deteriorated with worsening sepsis and metabolic acidosis and required admission to ITU for inotropic support. Once stabilised, a CT scan of her abdomen demonstrated a large right sided hydronephrosis (fig 3. Urine cultures were negative but blood cultures grew Escherichia coli. After 48 hours of intravenous cefuroxime and gentamicin she improved and was discharged to the ward.

Figure 3 Computed tomography. Expanded non‐enhancing right kidney consistent with pyelonephritis.

Discussion

TNF‐α is an inflammatory cytokine that is essential in defence mechanisms against sepsis. However, in inflammatory arthritis it is present in both joints and blood in high concentrations. The suggestion that TNF‐α is a critical cytokine in driving inflammatory diseases is supported by the success in blocking this cytokine. However, this may render the patient more prone to severe sepsis. Rheumatologists are aware of this, and screen patients for sepsis prior to starting the drugs, especially tuberculosis,⁴,⁵ and monitor patients for sepsis before each drug is given. Patients with a predisposition to infection or chronic infection are ineligible for anti‐TNF‐α therapy. The British Society for Rheumatology has drawn up guidelines for these issues.⁶

The patients presented here had delay in initial diagnoses. This might have resulted in a worse outcome or even death. We suggest that patients who have received anti‐TNF‐α therapy and develop non‐specific abdominal pain should proceed to urgent abdominal ultrasound or CT scan to exclude significant intra‐abdominal sepsis. A further concern is that anti‐TNF‐α drugs may diminish the acute phase response, so that significant sepsis may not always have dramatic or acute presentations. This may lull the attending doctor into a false sense of security. Doctors who encounter patients on anti‐TNFα therapy need to be aware of the possible complications. They should be treated as if they are significantly immunocompromised, and non‐specific symptoms such as abdominal pain need to be investigated intensively.