Correspondence: cytomegalovirus complicating inflammatory bowel disease: useful remarks.

We read with great interest the paper by Al-Zafiri and colleagues on cytomegalovirus (CMV) infection in inflammatory bowel disease (IBD).1 We believe, however, that the potential occurrence of CMV pneumonia in the course of CMV infection in patients with IBD—as well as the possible role of CMV in triggering hemophagocytic lymphohistiocytosis (HLH) in that context—also should have been considered. HLH is a potentially fatal hyperinflammatory syndrome that is characterized by histiocyte proliferation and hemophagocytosis. The most typical presenting signs and symptoms are fever, hepatosplenomegaly, and cytopenia. Less frequently observed clinical findings are neurologic symptoms, lymphadenopathy, edema, skin rash, and jaundice.2,3 Common laboratory findings include hypertriglyceridemia, hyperferritinemia, coagulopathy with hypofibrinogemia, and elevated transaminase levels.2,3 HLH should be diagnosed using clinical criteria developed by the Study Group of the Histiocyte Society (Table).4,5 Table. Hemophagocytic Lymphohistiocytosis (HLH) 2004 Diagnostic Criteria4,5 Two forms of the syndrome have been well characterized: familial HLH and sporadic HLH. The diagnosis of familial HLH requires either a positive family history of HLH or the presence of genetic mutations, such as aperforin gene mutations.6 A number of triggers have been related to the development of HLH, including viral infectious agents (particularly Epstein-Barr virus and CMV), bacteria, parasites (eg, Leishmania), fungi, and medications such as immunosuppressors.7-14 However, HLH may occur without any identifiable precipitating factor. We have addressed these issues in a recently published systematic review of the literature.15,16 In this review, the characteristics of 13 cases of CMV pneumonia in patients with IBD were described: fever and dyspnea were the most frequently reported symptoms, and diffuse bilateral infiltrates were the main radiologic findings. Moreover, an initial chest radiograph failed to identify signs of pneumonia in 2 patients. Six cases were complicated by HLH. Eight patients were transferred to intensive care units, and 4 of them (1 with HLH) died.15 Two cases of CMV pneumonia occurred in patients with IBD in deep remission.17,18 Patients with IBD are at increased risk for CMV infection due to a new infection or reactivation. Generally, CMV infection should be suspected in patients with IBD who present with severe and/or refractory intestinal disease. However, CMV infection in patients with IBD also can lead to atypical pneumonia. CMV pneumonia should always be suspected in patients with IBD who present with fever and tachypnea, especially if the latter is worsening and/or associated with dyspnea.16 Treatment must be early and specific. In the presence of cytopenia (affecting >2 lineages in the peripheral blood), a diagnosis of HLH should be suspected and may require combined antiviral and immunosuppressive treatment.