Cytomegalovirus (CMV) is a highly prevalent member of the herpesvirus family, also known as Human Herpesvirus 5 (HHV-5). Like other herpesviruses, CMV establishes a lifelong, latent infection in the host following initial exposure. For the vast majority of healthy individuals, this infection remains dormant and causes no noticeable symptoms or disease. However, in specific circumstances involving a compromised immune system, the virus can reactivate and spread throughout the body, leading to systemic disease. When this disseminated infection involves the skin, it produces a variety of lesions that can be an outward sign of serious internal illness.
Understanding the Appearance of Cutaneous CMV
The appearance of skin lesions caused by CMV is highly varied, a characteristic known as pleomorphism, which often complicates clinical diagnosis. One of the most common presentations in severely immunosuppressed adults is the formation of chronic, non-healing ulcers, particularly in the perianal or genital regions, or on the lower extremities. These ulcers can be deep and painful, often resisting conventional treatments until the underlying viral cause is addressed.
Other common manifestations include erythematous maculopapular rashes, which appear as flat, red patches interspersed with small, slightly raised bumps. The virus can also trigger vasculitis, an inflammation of the blood vessels, leading to purpuric rashes or petechiae. These small, non-blanching spots are caused by bleeding under the skin and signal damage to the dermal blood vessels.
Less frequently, CMV presents as firm, raised nodules or plaques that develop within the skin tissue. The varied nature of these lesions means that cutaneous CMV often mimics other common dermatological conditions, such as fungal infections or drug reactions. Because the appearance alone is rarely diagnostic, any new or persistent skin lesion in an at-risk individual should prompt an investigation for potential CMV involvement.
Populations Most Vulnerable to Skin CMV
Cutaneous CMV typically develops only in individuals whose immune systems are unable to contain the virus effectively. The majority of cases involving skin manifestations occur in two distinct groups: neonates with congenital infection and immunocompromised adults.
In newborns who acquire the infection before birth (congenital CMV), the virus can sometimes result in the “blueberry muffin baby” syndrome. This appearance is characterized by multiple reddish-blue spots, papules, and nodules scattered across the body. These lesions are a sign of systemic viral activity and often accompany other signs of infection, such as an enlarged liver and spleen.
The second, larger group is immunocompromised adults, particularly those with advanced Human Immunodeficiency Virus (HIV) infection or those who have received solid organ or hematopoietic stem cell transplants. In these patients, the medications used to prevent organ rejection or the underlying disease severely limit the body’s ability to control latent CMV. The appearance of skin lesions in this population, such as persistent ulcers, is a serious indication that the virus has reactivated and is spreading beyond its latency sites.
Identifying Cytomegalovirus in Skin Tissue
Because the clinical appearance of cutaneous CMV is non-specific, a definitive diagnosis requires laboratory confirmation, typically achieved through a skin biopsy. Histopathological analysis involves examining a tissue sample under a microscope, which often reveals the pathognomonic sign of CMV infection: the presence of “owl’s eye” inclusion bodies.
These distinct inclusion bodies are large, centralized intranuclear inclusions that appear within enlarged cells, particularly in the endothelial cells lining blood vessels or in fibroblasts within the dermis. The inclusion is dense, giving the appearance of a dark spot surrounded by a clear halo, resembling the eye of an owl. Finding these cytomegalic cells is highly specific for CMV infection, though they are not present in every case.
To increase diagnostic sensitivity, the tissue sample can undergo Polymerase Chain Reaction (PCR) testing. PCR is a highly sensitive molecular technique that detects the genetic material (DNA) of the CMV virus within the skin tissue, rapidly confirming the presence of the virus. Additionally, immunohistochemical staining can be performed to specifically visualize CMV proteins within the infected cells.
Antiviral Strategies for Managing Cutaneous CMV
The management of cutaneous CMV focuses on treating the underlying systemic viral infection, as skin involvement is a manifestation of disseminated disease. Treatment involves administering powerful antiviral medications to reduce the overall viral load in the body. The primary medications used are nucleoside analogues, specifically Ganciclovir and its oral prodrug, Valganciclovir.
Ganciclovir is often administered intravenously for severe, tissue-invasive disease like cutaneous ulcers to achieve high initial drug concentrations. Valganciclovir is frequently used for maintenance therapy or less severe cases due to its improved oral bioavailability. Treatment typically lasts several weeks or months, continuing until the lesions heal and the measurable viral load in the blood (viremia) is significantly reduced.
A concurrent and equally important part of the treatment involves managing the patient’s underlying immunosuppression. For transplant recipients, this may involve carefully reducing immunosuppressive drugs to allow the immune system to regain control over the virus. For patients with HIV, optimizing their antiretroviral therapy is paramount to strengthening their immune response against CMV.