CMV esophagitis is an infection of the esophagus, the muscular tube that carries food and liquid from the mouth to the stomach, caused by a virus called cytomegalovirus (CMV). The infection damages the lining of the esophagus and produces inflammation, usually in the form of deep ulcers.
CMV belongs to the herpesvirus family, and it is extremely common. Somewhere between half and four-fifths of adults have been infected at some point, usually in childhood or early adulthood and usually with no symptoms or only a mild flu-like illness. After that first infection, the virus is never cleared from the body; it remains permanently dormant inside certain cells, held in check by the immune system. Carrying CMV is therefore normal and is not a disease.
CMV esophagitis occurs when that dormant virus reactivates, which happens almost exclusively when the immune system is significantly weakened. The diagnosis therefore carries two pieces of information: there is an infection that needs treating, and there is a reason the immune system allowed it to happen. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.
CMV esophagitis is caused by reactivation of cytomegalovirus that has been dormant in the body since an earlier infection. Less often, it follows a first infection acquired from a transplanted organ or a blood transfusion. Once reactivated, the virus multiplies in cells of the esophageal wall and destroys them, and the surrounding tissue breaks down to form an ulcer.
Reactivation requires a substantially weakened immune system. The groups most affected are:
CMV esophagitis is uncommon in people with a normal immune system. It does occur occasionally in older adults, in people who are critically ill in intensive care, and in those with poorly controlled diabetes or kidney failure, but this is the exception. Where the infection appears without an obvious explanation, the care team will usually look for an undiagnosed cause, including testing for HIV.
The most prominent symptom of CMV esophagitis is pain on swallowing, called odynophagia, which can be severe enough to make eating and drinking difficult. Difficulty swallowing, chest pain behind the breastbone, and a sensation of food sticking are also common.
Because CMV reactivation is usually part of a wider illness rather than confined to the esophagus, general symptoms are frequent: fever, fatigue, poor appetite, nausea, and weight loss. Bleeding can occur from a deep ulcer, appearing as vomited blood, black stools, or unexplained anemia. Symptoms tend to develop over days to weeks rather than suddenly.
CMV esophagitis is diagnosed by taking tissue from the esophagus during an upper endoscopy, in which a thin flexible tube with a camera is passed through the mouth. The characteristic appearance is one or a few large, deep ulcers with sharply defined edges, most often in the middle or lower esophagus. These can be several centimeters across. The lining between them is often normal, which distinguishes this from infections that coat the whole surface.
Where the biopsies are taken from is unusually important in this infection, and it is worth understanding why. CMV does not infect the squamous cells that form the surface lining. It infects cells in the deeper tissue at the floor of the ulcer: the cells lining small blood vessels, and the fibroblasts that provide structural support. Biopsies must therefore be taken from the base or center of the ulcer, where those cells are exposed. This is the opposite of herpes esophagitis, where the virus infects surface cells at the ulcer edge. Multiple samples are usually taken from each ulcer, since infected cells can be sparse and scattered, and a negative biopsy does not entirely exclude the infection if the sampling missed them.
The tissue is examined by a pathologist, who looks for the changes described below. Because more than one infection can be present at the same time in someone whose immune system is suppressed, the samples are also examined for herpes virus and for fungal organisms.
When tissue from a person with CMV esophagitis is examined under the microscope, the pathologist looks for the distinctive changes the virus produces inside the cells it infects, known collectively as viral cytopathic effects. Findings that may appear on your report include:
Infected cells are often few in number and can be scattered thinly through a large area of damaged tissue, so the pathologist examines the sample carefully and may cut additional sections through the tissue before concluding that the virus is not present.
Because CMV-infected cells can be difficult to find, additional testing is often used to confirm or exclude the diagnosis. Results may appear on your pathology report or on separate laboratory reports.
Several infections can affect the esophagus, and more than one can be present at once in someone whose immune system is suppressed. Distinguishing them matters because each is treated with a different medication.
The outlook for CMV esophagitis depends far more on the state of the immune system than on the esophageal infection itself. With antiviral treatment the ulcers heal and symptoms resolve in most people, often over two to four weeks.
Complications arise mainly when treatment is delayed or when immune suppression is profound, and include bleeding from a deep ulcer, narrowing of the esophagus from scarring as ulcers heal, and rarely perforation or the formation of an abnormal connection to a neighboring structure.
The more important consideration is that CMV rarely confines itself to one organ. Reactivation in the esophagus frequently signals disease elsewhere, including the retina at the back of the eye, the colon, the liver, and the lungs. CMV retinitis can permanently damage sight and may cause no symptoms until vision is already affected, which is why an eye examination is often arranged. Relapse is common while immune suppression continues, and the durable solution is restoring immune function, whether by starting antiretroviral treatment for HIV or by adjusting anti-rejection medication after a transplant.
CMV esophagitis is treated with antiviral medication, and care is usually shared between the team managing the underlying condition and an infectious diseases specialist.
Ganciclovir given through a vein is the standard initial treatment. Once symptoms improve and swallowing is comfortable, this is commonly switched to valganciclovir, the same drug in a form that can be taken by mouth. Treatment usually continues for two to four weeks, and until the ulcers have healed and symptoms have resolved rather than for a fixed period. Both drugs can lower blood counts, so blood tests are monitored during treatment.
If the infection does not respond, resistance testing may be performed on the virus. Foscarnet and cidofovir are established alternatives, though both can affect the kidneys and require careful monitoring. Maribavir, an oral drug approved in 2021, is an option for transplant recipients whose infection has not responded to the standard drugs, with or without proven resistance.
Alongside antiviral treatment, attention turns to the immune system, since medication suppresses the virus but the immune system is what ultimately controls it. Where possible, immune-suppressing medication is reduced or adjusted, balanced against the risk of rejection or of the underlying disease flaring. For someone with HIV, starting or resuming antiretroviral treatment is the single most important measure. An eye examination is commonly arranged to check for CMV in the retina, and other organs are assessed if symptoms suggest involvement.
Follow-up depends on the situation. Blood viral load may be monitored to confirm the virus is being cleared, and a repeat endoscopy may be arranged if symptoms persist or if confirmation of healing is needed. For people who remain significantly immunosuppressed, ongoing preventive antiviral medication is sometimes used to reduce the chance of relapse.