Title : Tissue-invasive disease and cytomegalovirus: Cytomegalovirus trigger or killer? Two cases observed in an internal unit
Abstract:
Background: Human cytomegalovirus (CMV) is a Herpesviridae virus with a wide spectrum of pathology in humans. The major determinant of the clinical manifestation of CMV is host immunity and clinical manifestations can vary widely in the pratical setting. Immunocompetent patients generally has a benign and self-limited mononucleosis-like syndrome, whereas a tissue-invasive disease (an acute condition characterized by an uncontrolled overactivation of the immune system) is more frequent in immunocompromised patients. While polymerase chain reaction is a reliable detection test of CMV infection in the human host, the clinical value depends on a variety of factors : latent CMV, CMV infection, and CMV disease has different significance depending on the patient setting, and the decision to initiate antiviral therapy can be complex and patient-specific. Indeed in some of these conditions CMV is only a trigger, in others the etiology.
Case series: We present two cases:
- The first case is a 51 years old man, admitted to our Internal Medicine Unit for persistent fever, sore throat, arthralgia, weight loss, lymphadenopathy, severe acute hepatitis (biopsy performed, without CMV in histology), neutrophilic leukocytosis, hyperferritinemia.
A diagnosis of Still's disease was made (Yamaguchi criteria) and treatment with anakinra was performed. The significant elevation of CMV DNA determined the need for treatment with antivirals (ganciclovir), with control of viremia post-discharge A progressive clinical improvement occurred.
The major clinical hypothesis is that the inflammatory syndrome was triggered by CMV in an immunosuppressed patient.
- The second case is that of a 45-year-old woman, without apparent immunodeficiency conditions, who was admitted in our Internal Medicine Unit for fever, abdominal pain, severe splenomegaly with multiple splenic infarcts, high ldh, anemia. Multiple diagnostic tests were performed, including two bone marrow biopsies, a lymph node biopsy, a liver biopsy, autoimmune and infection tests, all negatives, except for the presence of high cmv dna in the blood.
Symptoms resolved with steroid and antiviral therapy with ganciclovir. Howewer during tapering of the steroid, gradual reappearance of symptoms (not fever, but asthenia) and anemia occurred. She was taking the steroid again with clinical benefit, except for mild dyspnea and hair loss. The PET scan with FPDG ,repeated after one month, showed several FDG-enhancing lymph nodes. The biopsy on peripheral lymph node with SUV 8 was negative. Finally the CT scan, done in suspicion of sarcoidosis, was negative for lymphadenopathy, but the patient has been on steroid therapy for months. The doubt of an inflammatory etiology (sarcoidosis?) and a lymphoma remains (negative histology, but during steroid therapy).
Steroid tapering was planned to do a new study.
At this moment the CMV seems the cause of the inflammatory picture in an immunocompetent patient, but it is not possible to exclude that it was a trigger of the disease.
Conclusion: In our two cases one of the main problems was to understand the role of CMV.
The most common clinical status of CMV in humans is latent infection and Mononucleosis-Like Syndrome, but also Tissue-Invasive Disease is described. Initial symptoms are often unspecific and similar to bacterial infections or sepsis or hematological diseases, as in our cases, so a rapid diagnosis, a fast diagnostic work, and initiation of treatment are important prognostic factors. After discussions and reasoning on the clinical case, both patients were treated with the antiviral: in the first case there was a total remission, in the second a partial remission. First-line treatment of CMV infection is ganciclovir or its oral prodrug valganciclovir. The importance of antiviral treatment is further highlighted when considering potential damage caused by long-term use of the immunomodulating treatment agents, as in our first patient. Indeed it is possible a reactivation of the triggering infection. It is important to understand in these situations whether CMV is a trigger or a cause of the inflammatory syndrome, since it changes the type of treatment of a pathology, which can be severe and life-threatening, especially in immunosuppressed patients
