ABSTRACT
We present a rare and unusual case of 22-year-old man who was on infliximab therapy for his uncontrolled ulcerative colitis. Infliximab was stopped as he didn't get any benefit from it and he ended up having subtotal colectomy and ileostomy. He presented with shortness of breath and eosinophilia and underwent a number of investigations and finally a diagnosis of chronic eosinophilia secondary to infliximab was made.
Introduction
Biologic agents are increasingly used for many autoimmune and inflammatory conditions, as they are both steroid sparing and can potentially induce and maintain remission. Notably tumour necrosis factor (TNF)-alpha antagonists are particularly useful in inflammatory bowel diseases (IBD) such as Crohn's and ulcerative colitis (UC).
Infliximab is a chimeric monoclonal antibody that targets TNF-alpha (a cytokine involved in modulation of inflammatory responses) and neutralises its effects. As infliximab is a generic TNF-alpha inhibitor and thus non-specific in its actions, it has the potential to cause immune-mediated side effects.1 The adverse pulmonary effects have been reported following infliximab infusion, including latent tuberculosis reactivation, invasive aspergillosis, interstitial pneumonitis, pulmonary oedema and alveolar haemorrhage.2–4
Case presentation
We present a case of 22-year-old man, who had never smoked, with background history of severe and difficult to control UC for which he was put on infliximab in December 2018 and received it until January 2019. He was not on any other medications. Since his UC flare ups were not controlled even with infliximab, he had subtotal colectomy and ileostomy in February 2019. He made an uneventful recovery and was discharged home.
He then presented to the emergency department with a 1-day history of shortness of breath and wheeze in May 2019. Vitals on presentations were blood pressure of 130/71 mmHg, pulse rate of 103 beats/minute, oxygen saturation of 89% on room air (RA), respiratory rate of 21 breaths/minute and afebrile. His UC was well controlled even without infliximab. He didn't have any courses of steroids since his surgery.
Bloods on admission showed microcytic anaemia (haemoglobin of 113 g/L; mean corpuscular volume of 67.9 fL), a raised D-dimer (1.53 mg/L) and a raised eosinophil count of 0.6×109/L (normal range 0.04–0.4), which had been normal previously. Rest of the routine bloods including urea, creatinine, electrolytes, C-reactive protein and liver function tests were all normal.
Arterial blood gases on RA were pH 7.46, partial pressure of carbon dioxide of 4.11 kPa, partial pressure of oxygen of 7.7 kPa, bicarbonate of 24 mEq/L, oxygen saturation of 87% and lactate of 1.1 mmol/L.
Chest X-ray on admission showed patchy interstitial shadowing in both lower lobes. Computed tomography pulmonary angiography (CTPA) showed no pulmonary embolism but patchy ground glass opacification at both lung bases. He was discharged with oral co-amoxiclav and clarithromycin.
He presented again to our hospital a month later with same symptoms. Haemoglobin was normal at 144 g/L but it showed raised eosinophils of 2.0×109/L. Rest of the bloods were unremarkable. He had a repeat CT of the chest, which showed new upper lobe and peripheral ground glass changes suggestive of disease progression. A respiratory opinion was sought at that time. Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies were carried out.
BAL showed 55% eosinophils, 30% mononuclear cells, 12% lymphocytes and 3% neutrophils. The airways appeared normal, with minimal secretions. Gram stain; bacterial, fungal and viral cultures; and special stains for Cytomegalovirus, Pneumocystis and acid-fast bacilli were negative. Transbronchial biopsy showed interstitial and intra-alveolar eosinophilic infiltrates.
There was no evidence of granulomas, vasculitis, fibrosis or interstitial lung disease. The case was discussed at multidisciplinary team meeting and the diagnosis of chronic eosinophilic pneumonia (CEP) was made. The patient was started on high-dose steroids and showed significant improvement clinically as well as radiologically (Fig 1). The patient was discharged home and is being followed up regularly in the respiratory clinic.
Computed tomography of the lung bases. a) Reticular nodular shadowing noted in lower zones. b) Almost complete resolution of reticular nodular shadowing in lower zones.
Discussion
This is a complex case of eosinophilic pneumonia in a patient who was on infliximab therapy. Our patient was thoroughly investigated for different causes of pulmonary eosinophilia including:
eosinophilic granulomatosis with polyangiitis: ruled out by negative anti-neutrophil cytoplasm antibodies (ANCA), no rash, no polyneuritis, no history of asthma and no vasculitis on biopsy
vasculitis: ruled out by negative anti-nuclear antibodies, ANCA, extractable nuclear antigen and no vasculitis on biopsy
atypical pneumonia: ruled out by negative screen
allergic bronchopulmonary aspergillosis: ruled out by normal Aspergillus specific immunoglobulin E (IgE), normal Aspergillus precipitins, IgE level of 215 IU/mL
infectious aetiologies: ruled out by negative stool studies for helminths and negative blood and bronchoalveolar lavage cultures for bacteria and fungi
Pneumocystis jirovecii pneumonia serology and serological testing for Strongyloides, Wuchereria and Schistosoma were negative; HIV and hepatitis serology were negative; avian antibodies were negative.
CT of the sinuses was normal. Lung function testing (Table 1) showed restrictive lung disease with reduced carbon monoxide transfer coefficient (69%) and transfer capacity of the lung for the uptake of carbon monoxide (45%) which improved tremendously after treatment (87% and 77%, respectively).
Pulmonary function test results
It was suspected that the cause of his eosinophilic pneumonia was infliximab. Infliximab antibodies were checked which were significantly raised at more than 200 IU/mL (normal range <20) even 6 months after stopping infliximab.
Conclusion
CEP is extremely rare and should be considered in patients receiving infliximab who develop eosinophilia, and pulmonary infiltrates with dyspnoea. Infliximab antibodies should always be checked before commencing infliximab therapy. To our knowledge there are only three reported cases of pulmonary eosinophilia with infliximab therapy, but all those patients developed eosinophilia acutely.5,6 Our patient developed symptoms 3 months after discontinuation of infliximab therapy. This makes it the first reported case of delayed reaction to infliximab leading to CEP.
- © Royal College of Physicians 2020. All rights reserved.
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