In the US, approximately 60–80% of the population has been exposed to cytomegalovirus (CMV) [1] [2]. CMV infection in the immunocompetent host is usually asymptomatic. However, it can also present with flu-like symptoms or more commonly, it can present as a mononucleosis syndrome [3] [4]. The illness is generally self-limited, with complete recovery over a period of days to weeks. Antiviral therapy is usually not indicated. The CMV complications can result in significant morbidity, including meningitis, encephalitis and pneumonitis; and thus, accurate diagnosis is necessary.

To our knowledge, there are few cases reported in literature demonstrating severe, multi-system CMV infection in previously healthy, immunocompetent hosts. These few reports describe CMV colitis and central nervous system (CNS) infection with sequelae such as meningitis and encephalitis [5]. A more recent case report describing CMV-induced colitis is illustrative [6].

This case report describes clinical, hematological and ocular manifestations of CMV infection in an immunocompetent, previously healthy, 19-year old male who acquired a CMV infection, possibly-although debatable- after being exposed to muddy flood waters, as a consequence of significant flooding in spring of 2010.

A 19-year-old Caucasian male was admitted to our medical-surgical floor with complaints of fever for two weeks and a papular rash five days prior that started on the trunk and extended to the extremities. Associated symptoms included nausea, vomiting, headache, dizziness, left flank pain, and periorbital swelling of the right eye. The patient denied any hiking activity, yard work, camping or tick bites. He denied sick contacts or new sexual partners. The patient affirmed that he had been working in muddy floodwaters, approximately one month prior to his developing symptoms and seeking treatment. Past medical history was significant for ADHD, for which the patient was taking dextroamphetamine. He had unremarkable social and family history.

Physical examination revealed a blood pressure of 122/66 mmHg, heart rate of 96 bpm, respiration rate 18/min; temperature 98.7°F. The patient was alert and oriented, but unwell. An erythematous morbilliform rash was present on the trunk and extremities. No lesions were observed on the palms or soles of the feet. An HEENT examination revealed a swollen, right, superior eyelid that was non-tender and non-purulent. No icterus, oral lesions, or pharyngitis was present. Cardiopulmonary examination was within normal limits. Abdominal examination revealed no hepatomegaly or splenomegaly. Costovertebral angle tenderness was noted on the left. No focal deficits were observed. Cranial nerves were grossly intact, and no meningismus was appreciated.

Laboratory findings demonstrated white blood cell count that was within a normal range (7.9/mm³); thrombocytopenia was present, with a platelet count of 74,000 and a lymphocyte percentage of 58; hemoglobin and hematocrit were 17.7 g/dL and 41.8%, respectively. A complete biochemistry panel was notable for elevated liver enzymes with an AST and ALT of 489 and 454 U/L, respectively. Alkaline phosphate was 417 U/L. Total bilirubin was 1.8 mg/dL and C-reactive protein was 51.6 mg/L. A urinalysis that was positive for bilirubin and ketones, but negative for nitrites or leukocyte esterase; urine culture was negative. Laboratory results further demonstrated a negative Epstein-Barr virus (EBV) panel, based on serological testing, influenza negative, according to rapid influenza diagnostic testing, gonorrhea and chlamydia by nucleic acid amplification test, negative,

A chest X-ray proved to be normal, and abdominal computed tomography showed mild hepatomegaly which was not detected on physical examination. The initial diagnosis that was assigned was fever of unknown origin, possibly attributed to a tick borne illness. The patient was treated for nausea with ondansetron; morphine, as needed (PRN) and ibuprofen for headache and flank pain. Hepatitis-A, B, and C, HIV and Borrelia Burgdorferi serology were ordered and subsequently negative. An infectious disease consult was requested RPR, EBV and leptospira test were either non-reactive or negative. CMV serology yielded positive results with CMV IgM and IgG both being elevated by serological methods. HHV-6, a close relative of CMV, was not investigated, and in retrospect, would have provided additionally-useful information, as a rash (and periorbital swelling) is an unusual symptom for CMV. A rash is more commonly related to HHV-6 but unfortunately, samples were not available for analysis. Follow-up CMV titers were also not obtained and could have proven useful. The patient's symptoms improved with supportive therapy, and he remained well during follow-up.

At least 60% of the US population has been exposed to CMV [7], with a prevalence of more than 90% in high-risk populations [8]. Demmler et al. [1] maintain that in developed countries, such as the United States or United Kingdom, as many as 60–80% of the population will be infected with CMV by adulthood.

The CMV manifestations in immunocompromised hosts have been widely documented, however, reports of those manifestations present in immunocompetent hosts are few and merit attention.

In the majority of hosts, primary CMV infection is clinically silent. When symptomatic, CMV disease in immunocompetent individuals may present as a mononucleosis syndrome or as flu-like symptoms. Individuals who are at increased risk for CMV infection include those who attend or work at daycare centers, persons who have multiple sex partners, and recipients of CMV mismatched organ or bone marrow transplants. Sexual activity may be an important risk factor for acquiring CMV infection, and its transmission by sexual acts has been well-documented [9] . The virus can spread by horizontal transmission (direct contact, person to person with virus containing secretions such as saliva, urine, cervical secretions or semen) or vertically via transplacental passage. Adolescence is another period of rapid acquisition of CMV. [10]

When CMV produces a mononucleosis-like syndrome, the most common manifestations are fever, fatigue, pharyngitis, adenopathy, and hepatitis. Headache, abdominal pain with diarrhea, arthralgias, and rash may also occur. Laboratory abnormalities include lymphocytosis or lymphopenia with thrombocytopenia and elevated transaminases. However, the heterophile antibody titers or monospot tests will be negative. This presentation fits closely with the presentation of the patient described in this case report. However, our patient presented with ocular symptoms, which are not frequently observed in these cases.

The confirmation of an acquired CMV infection is best accomplished by documenting a CMV IgG seroconversion with the presence of CMV IgM antibody. In our particular example, the patient had positive IgM and IgG antibodies. CMV cultures of the urine, saliva and blood may also be positive during the acute phase of the infection, but according to Fauci et al., the most sensitive way of detecting CMV in blood or other fluids may be by PCR [11]. The demonstration of the presence of CMV genome in blood by PCR would have been more helpful in defining the timing of infection in this case. Stagno et al., maintain that a positive IGM can persist up to one year after infection [12]. Irrespective of the detection methods used, we were, unfortunately, unable to categorically determine that the patient's source of infection was attributed to flood waters and could only highlight an association, in a speculative manner.

Subclinical transaminitis is the most common finding in immunocompetent patients; elevations of alkaline phosphatase and total bilirubin are less typical [4]. The patient in this report had both transaminitis and elevations in total bilirubin and alkaline phosphatase. The patient improved with supportive therapy. Our case highlights a source of potential CMV infection that is not widely reported; although, an alternative cause cannot be excluded. Further, this immunocompetent patient presented with atypical signs of systemic CMV infection, including periorbital swelling, thrombocytopenia and dark urine with hepatosplenomegaly on imaging.

In conclusion, our case presents a case of severe CMV infection possibly related to flood water exposure-although debatable- and highlights the need to consider CMV infection as a cause for the presenting symptoms described herein, in immunocompetent patients.

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