Learning point for clinicians
We recommend Inflammatory Bowel Disease patients should have full viral serology testing prior to commencing immunosuppressive agents. While vaccinations are not available for all viruses, it highlights at-risk patients and may result in earlier detection and treatment. Primary infection with cytomegalovirus while immunosuppressed carries a significantly greater morbidity and mortality. In this case, had this patient’s CMV status been known, she would have flagged as high risk for primary CMV infection, possibly leading to earlier intervention.
Case
A 35-year old lady presented with a 1-week history of a febrile illness without localizing symptoms or signs. She was on azathioprine 200 mg monotherapy for treatment of terminal ileum Crohn’s Disease diagnosed 3 years previously. She attended for 3 monthly phlebotomy which document a baseline lymphopenia, averaging at 1.4. She was an active smoker, 20 pack years. She had no other medical history, no excessive alcohol intake and no infectious contacts or risk factors for Tuberculosis. On examination, the patient was febrile, 39.5, tachycardia of 126, normotensive and saturating to 98% on room air. She had a BMI of 38 and examination was otherwise normal.
Investigations revealed a mild thrombocytopenia with platelets of 129, white cell count of 3.7, with lymphopenia of 0.7. Liver function tests were mildly deranged and C related protein was elevated to 114.7. Chest X-ray and ultrasound abdomen on admission were normal. CT abdo-pelvis showed a featureless ascending colon with combing of the terminal ileal and caecal mesentery suggesting a chronic inflammatory process. Azathioprine was held on admission.
The patient was treated as a likely viral infection and additionally covered with intravenous antibiotics. She continued to suffer persistent temperatures of up to 40.4 Celsius. Unfortunately, the patient deteriorated on day 6 with worsening thrombocytopenia and leukopenia. She was treated with one dose of G-CSF and a colonoscopy to rule out CMV colitis was performed which was normal with normal biopsies. The terminal ileum was not intubated or biopsied at this time. On the same day, the patient developed respiratory distress with a respiratory rate of 34, peak expiratory flow rate of 220 ml/min. Repeat CXR showed a new right upper lobe lesion. While viral serology was still pending, due to clinical suspicion and clinical deterioration, the patient was started on empirical ganciclovir therapy for CMV pneumonitis.
CT pulmonary angiogram on the same day showed multifocal airspace disease predominantly in the right upper lobe with small bilateral pleural effusions likely infectious or inflammatory in origin, Figure 1(A). CMV IgM and IgG were subsequently positive suggesting primary infection within 3 months. CMV PCR was 20 205 copies/ml.
Figure 1.
(A) CT pulmonary angiogram showing multifocal airspace disease predominantly in the right upper lobe with small bilateral pleural effusions likely infectious or inflammatory in origin. (B) Serial CMV PCR DNA viral load.
On day 2 of treatment, she required intubation and admission to ICU. She had a stormy ICU admission requiring hemodialysis for maintenance of fluid and electrolyte balance. Further investigations included a bronchoscopy to rule out superimposed tuberculosis and atypical infections, which was clear. Unfortunately, her ICU admission was complicated by acute respiratory distress syndrome, bacterial pneumonia and a duodenal ulcer. She became increasingly difficult to ventilate. In total, the patient required 25 d on ganciclovir and was intubated for 20 d. On day 30 of admission, the patient was discharged to the ward and ganciclovir was discontinued once viral load was not detected, Figure 1(B).
Discussion
This case demonstrates the risks exposed to immunosuppressed patients. Although CMV colitis is a well-recognized complication, CMV pneumonitis not as common and should be considered early in the differential for a patient with non-localizing signs and symptoms. While CMV pneumonitis is rarely diagnosed in the immunocompetent patient,1 it is a well-documented complication in both AIDS and transplant patients. There have also been prior incidences of CMV pneumonitis in Crohn's disease patients while on azathioprine.2
ECCO guidelines for systemic CMV infection in IBD patients advise 2–3 weeks of ganciclovir therapy and discontinuation of immunosuppressant agents.3 Literature for CMV pneumonitis is limited and thus mortality and morbidity are difficult to surmise. A systematic review of CMV pneumonitis in IBD patients found 8 out of 13 patients requiring ICU admission and a mortality rate as high as 4 out of 13 patients.4
Conflict of interest: None declared.
References
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