In response to a question yesterday about ‘what does CMV infection mean?‘. Yes, in the small print of the AAN poster I mentioned yesterday the estimated incidence of cytomegalovirus infection on alemtuzumab treated patients is 0.13%. CMV infection has only been identified with alemtuzumab and HSCT and is not, to the best of my knowledge, associated with other DMTs. CMV reactivation typically occurs with quite marked immunosuppression that hits both innate (neutrophils and monocytes) and adaptive (T-cells) immunity. We have only had one patient at our centre with this complication and this patient did not have MS, but a condition called CNS vasculitis. He presented with a pyrexia and a pneumonia, about a week after have alemtuzumab treatment. He responded rapidly to ganciclovir treatment and made a full recovery.
Background: Human cytomegalovirus, or CMV, is a member of the herpes virus family. CMV infection is typically asymptomatic in healthy people, but can be life-threatening in immunocompromised people. After infection, CMV remains latent within the body throughout life and like other herpes viruses can be reactivated at any time. CMV is strongly associated with mucoepidermoid carcinoma and possibly other malignancies. CMV is found throughout the world and all socioeconomic groups, and infects between 60% and 70% of adults in developed countries and almost 100% in emerging countries.
As with all herpes viruses CMV has genes dedicated to altering and/or evading innate (hard-wired) and adaptive (memory) immunity. The immune system has a lifelong battle with CMV and as we get older a large number of your peripheral T-cells, or T-cell repertoire, becomes dedicated to keeping CMV in check. CMV is the virus most frequently transmitted to the developing foetus and can cause congenital CMV infection, which is one of the leading causes of deafness, learning disabilities, and intellectual disability in children.
Clinical features of CMV reactivation: CMV infection post-alemtuzumab is usually due to reactivation of latent virus and not new infection. Reactivated CMV infection can affect different parts of the body:
- Retina: CMV retinitis affects the eyes and can cause blindness.
- Lungs: CMV pneumonia caused by CMV can be life threatening.
- GIT: CMV can affect any part of the gastrointestinal tract, including the esophagus, stomach, liver, gall bladder, pancreas and colon, causing ulcers, liver inflammation, intestinal obstruction and colitis. Symptoms can include painful and difficult swallowing, nausea, vomiting, abdominal pain, yellow skin (jaundice) and watery or bloody diarrhoea.
- Brain: CMV can infect the brain and other parts of the nervous system, causing symptoms like headache, confusion, and leg weakness.
Diagnosis: The diagnosis of CMV usually requires a detailed physical and targeted tests depending on which part of the body is infected. Typically the virus is detected in the blood, urine and/or stools. Occasionally, a biopsy of the affected organ, such as the lung or colon, is needed to confirm the diagnosis. Retinal involvement is usually typical and most ophthalmologists suggest the diagnosis based on the retinal examination.
|CMV retinitis displaying frosted branch angiitis|
Treatment: CMV reactivation is usually treated with anti-viral agents including ganciclovir, valganciclovir, cidofovir and foscarnet. Ganciclovir can be given intravenously, orally or as a pellet implanted in the eye to treat an infection in the retina. Valganciclovir has better oral absorption than ganciclovir but the two medications are otherwise very similar. Cidofovir is approved from treatment of CMV retinitis. Foscarnet must be given intravenously and is usually reserved for those who have virus that is resistant to ganciclovir or those who have serious side effects from ganciclovir. Side effects of ganciclovir and valganciclovir include the suppression of white blood cells, red blood cells and platelets. Because cidofovir and foscarnet can cause renal toxicity, kidney function needs to be monitored carefully.
The following are guidelines for alemtuzumab associated CMV reactivation. Please note that the severity of CMV reactivation in pwMS treated with alemtuzumab is likely to be less severe than that which occurs alemtuzumab-treated cancer patients and those undergoing HSCT.