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Tumour necrosis factor α (TNFα) antagonists have been associated with reactivation of tuberculosis and development of other opportunistic infections.1–4 We have recently observed a case of septic arthritis caused by Moraxella (Branhamella) catarrhalis in a patient treated with infliximab that we describe briefly here.
The patient, a 45 year old man, was referred to us in September 1999 for evaluation of an eight year history of recurrent episodes of arthritis of the knees and elbows and of recurrent episodes of inflammatory swelling with pitting oedema over the dorsum of the hand. One year before the onset of arthritis he had undergone replacement surgery for an insufficient aortic valve. Physical examination disclosed swelling, effusion, and tenderness in the right knee, together with tenosynovitis of the left tibialis posterior and flexor digitorum longus. Spine movement was not limited and chest expansion was not restricted. Routine laboratory evaluation was normal and HLA typing was positive for B27. Radiographs of the knees showed only soft tissue swelling, and pelvis and spine radiographs were normal. The were no symptoms of gut disease, and ileocolonoscopy was not performed. Our diagnosis was undifferentiated spondarthritis (uSpA).
In the following months the patient developed severe recurrent episodes of peripheral arthritis, peripheral enthesitis, and tenosynovitis. At the beginning he was treated with steroid injections, non-steroidal anti-inflammatory drugs, and short courses of oral steroids. In the following months he was given sulfasalazine, cyclosporin A, and methotrexate, with no improvement.
In May 2002, because of the severity of the clinical situation, we decided to treat the patient with infliximab, after obtaining his informed consent. He received the drug at a dose of 5 mg/kg by intravenous infusion at 0, 2, and 6 weeks. A fourth infusion was given two months after the third one. The improvement was only partial. The patient continued to have less severe peripheral manifestations of spondarthritis.
In October 2002, one month after the fourth infusion, he presented with a severe arthritis of the right knee. He denied any airway complaints. Arthrocentesis yielded 50 ml of purulent fluid. Laboratory evaluation showed only an erythrocyte sedimentation rate (ESR) of 95 mm/1st h and a C reactive protein (CRP) level of 172 mg/l (normal <5). Earlier values were 2 mm/1st h and 0.7 mg/l, respectively. Culture of the purulent synovial fluid grew Moraxella catarrhalis, and the blood culture was negative. The infection was cured with a two week course of antibiotic treatment with ciprofloxacin at a dosage of 1 g/day and teicoplanin at a dose of 200 mg/day. Joint drainage was performed on two occasions. The ESR was 2 mm/1st h and CRP was 20.5 mg/l after the end of treatment.
Both the two TNFα antagonists, the mouse-human monoclonal IgG1 monoclonal antibody infliximab and the 7 kDa IgG1 recombinant fusion protein etanercept, have been shown to be effective in ankylosing spondylitis and psoriatic arthritis.5,6 Severe uSpA, unresponsive to sulfasalazine, is another possible indication for TNFα neutralising treatment.7 Our patient with severe uSpA unresponsive to sulfasalazine and methotrexate partially improved with infliximab. Unfortunately, the drug was stopped owing to the infection caused by Moraxella catarrhalis.
Opportunistic infections, including tuberculosis,1 aspergillosis,2 listeriosis,3 and histoplasmosis,4 are potential complications of treatment with TNFα blocking agents. Moraxella catarrhalis, a component of the normal bacterial flora of the upper airways and possibly the female genital tract, has recently emerged as a cause of different illnesses, including sinusitis, otitis media, conjunctivitis, laryngitis, bronchitis and pneumonia, and systemic infections in immunocompromised patients.8 There are also reports of septic arthritis due to Moraxella catarrhalis.9,10 Our patient developed Moraxella catarrhalis arthritis after the third infusion of infliximab. He was immunocompromised also because he had received immunosuppressive disease modifying treatment with methotrexate in the eight months before beginning the anti-TNFα blocking therapy.
In conclusion, we suggest that Moraxella catarrhalis should be included in the list of opportunistic organisms inducing infection associated with anti-TNFα blocking therapy.
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