Letter to the Editor
Severe CMV-related pneumonia complicated by the hemophagocytic lymphohistiocytic (HLH) syndrome in quiescent Crohn's colitis: Harmful cure?
Article first published online: 8 AUG 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 17, Issue 11, pages E145–E146, November 2011
How to Cite
Presti, M. A. L., Costantino, G., della Torre, A., Belvedere, A., Cascio, A. and Fries, W. (2011), Severe CMV-related pneumonia complicated by the hemophagocytic lymphohistiocytic (HLH) syndrome in quiescent Crohn's colitis: Harmful cure?. Inflamm Bowel Dis, 17: E145–E146. doi: 10.1002/ibd.21828
- Issue published online: 10 OCT 2011
- Article first published online: 8 AUG 2011
- Manuscript Accepted: 20 JUN 2011
- Manuscript Received: 14 JUN 2011
To the Editor:
In April 2009, a 32-year-old female was diagnosed with Crohn's colitis; her history was positive for psoriasis and a cesarean section. The patient responded well to prednisone and a subsequent induction therapy with infliximab (5 mg/kg, three infusions); thereafter, she was set on azathioprine maintenance treatment (2.2 mg/kg/day). Eight months later, while in perfect clinical and biochemical remission, she developed high-grade fever (39.5°C) and was admitted on the third day to our unit.
On admission, her temperature was 38.8°C, pulse rate 112 bpm, respiratory rate 35 breaths/min, and oxygen saturation of 82% on room air. The spleen was palpable 2 cm under the costal margin. The rest of the physical examination was unremarkable. Blood parameters showed pancytopenia (hemoglobin 8.1 g/dL; leukocytes 1260 el/μL x, platelets 53,000 el/μL), high levels of C-reactive protein, absent NK activity, hypertriglyceridemia (426 mg/dL), and high values of serum ferritin (1260 μg/L).
A chest film revealed bilateral infiltrates (Fig. 1A) and an ultrasound evaluation of the abdomen was negative except for a slightly enlarged spleen. Blood and urine cultures as well as serology for a number of viral and bacterial pathogens was performed and a combined broad spectrum antibiotic and antifungal treatment and methylprednisolone (20 mg/day) was started. On the second day she was transferred to the ICU because of increasing respiratory distress. Blood and urine culture were negative for bacteria and fungi. Serological studies for leishmaniasis, parvovirus B19, and human immunodeficiency virus (HIV) were negative. Polymerase chain reaction on peripheral blood was positive for CMV (2670 gEq/100,000 cells), while it was negative for human herpes virus (HHV)-6, HHV-8, and Epstein–Barr virus (EBV). Adding ganciclovir (5 mg/kg b.i.d. i.v.) to therapy the clinical picture improved within 20 days and the patient was discharged after a final control chest film (Fig. 1B) on oral valganciclovir (450 mg b.i.d.) until repeated negative results for CMV and normalization of peripheral lymphocyte subpopulations. After 1 year the patient is still in clinical remission without any therapy.
Systemic infections due to CMV are well known in patients with inflammatory bowel disease (IBD), but usually associated with acute flares of disease and additive antiviral therapy improves outcome of colitis.1, 2 Screening for latent CMV infection before immunosuppressive therapy is usually not recommended.3 In our patient with Crohn's colitis, CMV pneumonia developed while under thiopurine monotherapy and in deep clinical remission similar to a case described several years ago in a patient under 6-mercaptopurine (6-MP).4 In our case the clinical course was complicated further by the HLH syndrome diagnosed on the basis of the HLH 2004 criteria (Table 1). Besides the genetically linked forms, HLH has been found to be associated with autoimmune disorders and may be precipitated by several drugs including infliximab and azathioprine or by various infective agents, including CMV, EBV, and HHV-6.5 A review by James et al7 in 2006 reported on seven cases of HLH in IBD patients with a mortality rate that reached 30%. The authors suggested that immunosuppressive therapy could lead to this inappropriate macrophage activation in genetically susceptible patients. After this review an additional 11 cases from seven different countries were described including the present, 2 of 11 with fatal consequences.7–14 As in our case careful monthly monitoring of immunosuppressive therapy could not prevent this very serious, potentially lethal adverse event. Gastroenterologists should be aware of this complication which presents with an apparently rising frequency.
|The diagnosis of HLH can be established if one of either 1 or 2 below is fulfilled:|
|1. A molecular diagnosis consistent with HLH|
|2. Diagnostic criteria for HLH are fulfilled (five out of the eight criteria below):|
|• Cytopenias (affecting ≥2 or 3 lineages in the peripheral blood):|
|Hemoglobin < 90 g/l (in infants< 4 weeks: hemoglobin <100 g/l|
|Platelets < 100.000/ml|
|Neutrophils < 1000/ml|
|• Hypertriglyceridemia and/or hypofibrinogenemia:|
|Fasting trigycerides≥265 mg/dl|
|Fibrinogen ≤ 1.5 g/l|
|• Hemophagocytosis in bone marrow or spleen or lymph nodes|
|• Low or absent NK-cell activity|
|• Ferritin ≥ 500 μg/l|
|• Soluble CD25 ≥ 2400 U/l|
|• Supportive clinical criteria include neurologic symptoms and cerebrospinal fluid pleocytosis, conjugated hyperbilirubinemia, and transaminitis, hypoalbuminemia, and hyponatremia|
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Maria A. Lo Presti MD*, Antonio Cascio MD, Giuseppe Costantino MD*, Anna della Torre MD*, Alessandra Belvedere MD*, Walter Fries MD*, * Dip. di Medicina Interna, University of Messina, Messina, Italy, Dip di Patologia Umana, University of Messina, Messina, Italy.