Valganciclovir as Treatment for Cytomegalovirus Disease in Solid Organ Transplant Recipients

Kumar

Texas Heart Institute Journal

2014

W e present a rare case of fulminant myocarditis caused by a cytomegalovirus (CMV) infection in an immunocompetent patient-an infection that oral valganciclovir therapy resolved in a dramatic clinical and immunologic manner. Cytomegalovirus infection occurs primarily in the setting of advanced immunosuppression (for example, among human immunodeficiency virus [HIV] patients and organ-transplant recipients) and is typically a reactivation of latent infection. Cytomegalovirus infection in an immunocompetent host is generally asymptomatic; or it might present as a mild, self-limiting, heterophile-negative, mononucleosis-like syndrome. Occasionally, primary CMV infection in immunocompetent hosts can lead to severe organ-specific complications, significant morbidity, and death.1 In a 2008 review 2 of the medical literature, which examined 290 immunocompetent adults with severe CMV infection, the most frequent sites involved were the gastrointestinal tract (colitis) and the central nervous system (meningitis, encephalitis, and transverse myelitis), followed by the blood (hemolytic anemia and thrombocytopenia), the arterial or venous system (thrombosis), the eyes (uveitis), and the lungs (pneumonitis). In contrast, CMV myocarditis and pericarditis in an immunocompetent host are extremely rare entities: few cases have been reported to date. [3][4][5][6][7][8][9][10][11][12][13] It is quite possible that the true number of CMV myocarditis cases is underreported, because most cases are self limiting and underdiagnosed. Case ReportIn January 2013, a 72-year-old previously healthy white woman was hospitalized for high-grade fevers (2-week history) unresponsive to acetaminophen and for profound weakness, myalgia, headaches, and poor oral intake. She reported no recent contact with sick people or animals, no recent history of travel, no history of blood-product transfusion, and no smoking, alcohol, or recreational drug use. Her medical history was significant for hypothyroidism treated with levothyroxine. Examination at presentation was unexceptional apart from high-grade fevers up to 104 °F.Her initial laboratory studies showed a white blood cell count of 7.6 ×10 3 /µL (normal range, 4-11 ×10 3 /µL) with a lymphocyte count of 66% (normal range, 20%-53%). Her C-reactive protein level was 11 mg/dL (normal, ≤0.49 mg/dL). Her liver enzymes on admission were elevated: alkaline phosphatase, 201 U/L (normal range, 20-140 U/L); aspartate aminotransferase, 171 U/L (normal range, 5-40 U/L); and alanine aminotransferase, 162 U/L (normal range, 5-40 U/L). Her bilirubin lev-

Section: Discussionmentioning

confidence: 99%

Fulminant Cytomegalovirus Myocarditis in an Immunocompetent Host: Resolution with Oral Valganciclovir

Kumar

Texas Heart Institute Journal

2014

American Journal of Transplantation

“…(18,19). However, existing studies have primarily comprised small sample sizes and previous meta-analyses have excluded valganciclovir (1,2,20,21 (22,23,(26)(27)(28)(29)(30)(31)(32)(33)(34) (Table 1). The follow-up duration was a minimum of 12 months after transplantation in all but three studies (29,30,33 (27,28,32).…”

Section: Cytomegalovirus (Cmv) Is An Important Opportunistic Pathogenmentioning

confidence: 99%

“…Similarly, the threshold of DNAemia by CMV DNA PCR to initiate preemptive treatment varied from ≥15 to ≥2000 copies/mL (23,(27)(28)(29)(32)(33)(34). In all, three studies monitored for antigenemia or DNAemia for 3 months, 2 for 6 months, 2 for 12 months, and 1 for 4 months posttransplant (22,23,(26)(27)(28)(29)(30)(31)(32) (22,23,(27)(28)(29)(30)(31)(32)(33)(34). Six of the nine studies described explicitly the relationship between preemptive therapy and subsequent development of CMV disease (22,23,27,30,31,33,34) (22,23,26,27,(29)(30)(31)(32)(33).…”

Section: Cytomegalovirus (Cmv) Is An Important Opportunistic Pathogenmentioning

confidence: 99%

Prevention of Posttransplant Cytomegalovirus Disease and Related Outcomes with Valganciclovir: A Systematic Review

Sun

Wagener

Singh

2008

108

The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT recipients were synthesized for descriptive analysis. CMV disease occurred in 2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and prophylaxis, respectively. Although the incidence of early-onset (≤90 days posttransplant) CMV disease was only 0.8% and 1.2% in all patients and R-/D+ patients receiving valganciclovir prophylaxis, the incidence of late-onset (>90 days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic group, respectively. On the contrary, no patients developed late-onset CMV disease in preemptive group. Both approaches with valganciclovir have successfully decreased CMV disease in SOT recipients. Late-onset CMV disease is a complication observed uniquely with valganciclovir prophylaxis, particularly in R-/D+ patients, but not with preemptive therapy.

GE Port J Gastroenterol

“…Because of its high bioavailability, p.o. valganciclovir is also considered an effective drug [7] . Maintenance therapy with oral valganciclovir is advocated in particular situations, such as in patients with concomitant CMV retinitis and in those receiving high-dose immunosuppression [24,25] .…”

Section: Discussionmentioning

confidence: 99%

“…ganciclovir or per os (p.o.) valganciclovir is successful in most cases [5][6][7] . Nonetheless, GI CMV can cause serious disease in immunocompromised patients and has been associated with significant morbidity and mortality [8,9] .…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus Disease of the Upper Gastrointestinal Tract: A 10-Year Retrospective Study

Marques¹,

Carmo²,

Gomes

et al. 2017

Background and Aims: Cytomegalovirus (CMV) disease of the gastrointestinal (GI) tract is a major cause of morbidity and mortality in immunocompromised patients. The colon is the most commonly affected site, and the literature is scarce regarding CMV disease of the upper GI tract. Therefore, our study aimed to evaluate the clinical and endoscopic features of upper GI CMV disease. Methods: This 10-year retrospective study included all patients with a histopathological diagnosis of upper GI CMV infection. Patients' clinical, endoscopic, therapy, and follow-up data were collected from medical records. Results: Twelve patients with histopathologically proven upper GI CMV disease were identified (age 61 ± 18 years, 50% men). Most of the patients were immunocompromised (75%) due to acquired immunodeficiency syndrome (AIDS), malignancy, and/or immunosuppressive therapy. In the remainder (25%), the disease occurred in the absence of immunodeficiency and immunosuppression. Three patients (all with AIDS) presented with disseminated CMV infection. In the majority of the cases (83%), upper GI CMV disease was symptomatic, and the most common clinical presentations were odynophagia/dysphagia (25%) and nausea/vomiting (25%). Endoscopically, there were 5 cases of esophagitis (42%) and 7 cases of gastritis (58%). The lower esophagus (33%) and the gastric antrum (42%) were the most frequently affected GI sites. Regardless of the location, mucosal ulceration was the most common endoscopic finding (75%) and was associated with very deep ulceration resembling cavitation in 2 cases. Other endoscopic features were mucosal edema, hyperemia, and nodularity (25%). Eleven patients (92%) received antiviral treatment (duration 26 ± 12 days). The 1-month and 1-year mortality rates were 16.7 and 25%, respectively. Conclusions: Upper GI CMV disease can occur in the absence of immunodeficiency and immunosuppression. It is usually symptomatic, and mucosal ulceration is often evident at endoscopy. It is associated with significant mortality; therefore, early diagnosis and adequate antiviral treatment are essential.