At the moment, viruses are playing a major role in our lives. Therefore, it might be the right time to turn to another interesting virus. It plays a particularly important role in MS patients who are (highly effectively) treated with immunotherapy – more important than the coronavirus: the Varicella Zoster Virus (chickenpox virus). The virus that causes herpes zoster (= shingles) is the chickenpox virus. Its technical term is Varicella Zoster Virus (VZV). The Varicella Zoster Virus belongs to the group of herpes viruses, such as the Herpes Simplex Virus Type I (HSV I), the causative agent of “cold sores” or the Epstein-Barr Virus (EBV), the causative agent of glandular fever (infectious mononucleosis). The viruses of the herpes group are DNA viruses, i.e. they contain their genetic material in the form of double-strand DNA (unlike the coronavirus, which is an RNA virus), and are larger and more complex than, for example, the now well-known SARS-CoV2.
Herpes viruses are lifelong companions
Herpes viruses are clinically extremely significant and can cause a variety of different diseases. What they all have in common is the ability to reactivate from latency. That is, despite the presence of neutralizing antibodies and cytotoxic T-cells, all viruses of the herpes group remain in our organism for life and can reactivate and cause a new disease if the immune system is “careless”. While this reactivation is usually locally limited in immunocompetent individuals, reactivation is feared in immunodeficiency because life-threatening complications can also occur in this context.
The special properties of herpes viruses explain why Varicella Zoster viruses lead to a chickenpox disease in children, but to shingles (= herpes zoster) in adults, especially in older age. The Varicella Zoster Virus is highly contagious. In my childhood, when there was no vaccination against it, it was quite likely that you would get infected with chickenpox as a child. If you were lucky, you had no or only mild symptoms. If you were unlucky, your whole body was covered with weeping and itching blisters. I was unlucky…
Immune system cannot eliminate Varicella Zoster Virus
In healthy children, the immune system copes well with the virus. Cytotoxic T-cells and neutralizing antibodies are formed and after about two weeks the whole spook is over. However, as already mentioned above, the immune system is not able to eliminate the virus. Under the pressure of the immune system, the Varicella Zoster Virus simply retreats and persists (guarded by the immune system) preferentially in the cells of the sensitive spinal ganglia.
After a years-long rest period (latency phase), various factors that influence the cellular immune system can lead to a local reactivation. This local reactivation takes place in the spinal nerve segment where the Varicella Zoster Virus has “overwintered”. In the affected skin area, clear, grouped blisters form which crust over in the course of time. However, since this is effectively an infectious disease of the spinal nerve, shingles are very painful, sometimes for months, and are often associated with systemic symptoms such as fever and fatigue. By the way, adults with shingles can infect children who have not yet been immune or vaccinated, who can then contract chickenpox.
Risk factors for reduced reactivity of the immune system
The main risk factor for reduced reactivity of the cellular immune system is primarily older age. Then the immune system is generally not so reactive. But also stress, strong sunlight or a confrontation with another pathogen (e.g. a urinary tract infection) affect the immune system. In the context of MS, however, it is mainly certain MS medications that can impair the reactivity of the immune system to the Varicella Zoster Virus. These are less the moderately effective drugs like interferons, glatiramer acetate, dimethyl fumarate or terflunomide, but rather the highly effective substances like cladribine, alemtuzumab and the S1P modulators (fingolimod, ozanimod, siponimod). Especially the MS drugs whose mechanism of action targets T-cells. In B-cell-depleting therapies (rituximab, ocrelizumab, ofatumumab), herpes (re)infections were not a major problem. (An overview of currently available MS therapies, their mode of action and side effects is provided by “Treating Multiple Sclerosis”.)
Check Varicella Zoster Virus status before MS therapy with highly effective drugs
For the reasons mentioned, it is therefore extremely important, especially with the aforementioned highly effective MS therapies, to check whether there is already immunity to the Varicella Zoster Virus, or whether vaccination was given in childhood. If this is not the case, therapy cannot begin before the completion of a vaccination against the Varicella Zoster Virus (note: this is a live vaccine). In addition, one should be aware of shingles as a side effect of MS therapies. With Lemtrada, a prophylaxis with an antiviral drug is routinely given in the first weeks after infusion. If herpes reactivations occur frequently, discontinuation of the preparation must be considered.
Given the importance of herpes zoster as a medical complication in old age and under immunotherapy, it is a very positive development that a vaccination against herpes zoster (a dead vaccine – not to be confused with the vaccination against the Varicella Zoster Virus for children) is now available. I had already reported on this. Shingix (the trade name of the vaccine) has a STIKO (Permanent Vaccination Commission) recommendation for normal persons from 60 years and for patients with autoimmune diseases from 50 years, so it is covered by insurance. However, the vaccine has already been approved from the age of 18 and I strongly hope that the STIKO will reconsider its decision and recommend the vaccine also for MS patients and other chronically ill people from the age of 18.
This blog post is also intended to show that it is not new to plan MS therapies considering viruses – SARS-CoV2 is just another candidate.
