Chickenpox is a self-limiting disease

Early therapy prevents complications

Dangerous interaction

 

It is important to note the serious interaction between brivudine and fluoropyrimidines. If brivudine and fluorouracil are combined, this leads to an accumulation of fluorouracil and consequently nausea, vomiting and diarrhea. In severe cases, bone marrow depression with neutropenia occurs, which can lead to sepsis and death within a few days.

 

A pharmacokinetic interaction is responsible for these serious side effects. Brivudine irreversibly inhibits dihydropyrimidine dehydrogenase (DPD) via its main metabolite bromovinyluracil; this enzyme is responsible for more than 80 percent of the breakdown of fluorouracil in the liver. There is an accumulation of fluorouracil in the body and thus increased toxicity.

 

Brivudine (example: Brivex®) is rapidly absorbed (maximum plasma level one hour after ingestion) and rapidly metabolized. The irreversible inhibition of DPD occurs within a few hours. The enzyme only regains its full functionality 18 days after taking the last dose of brivudine. Other systemically applicable fluoropyrimidines, for example capecitabine (example: Xeloda®), Flucytosine (example: Ancotil®), Floxuridine (example: FUDR®) and Tegafur plus uracil (example: UFT®), as well as the local application of fluorouracil (example: Verrumal®, Efudix®) are affected by this interaction.

 

In practice, the following applies: A combination of brivudine with fluorouracil and its prodrugs is absolutely contraindicated. There must be an interval of at least four weeks between the treatment of brivudine and a fluoropyrimidine. This also applies to locally used fluorouracil.

 

Pain management

 

For the treatment of lighter pain in the acute stage, analgesics and non-steroidal anti-inflammatory drugs such as paracetamol, ibuprofen or diclofenac are suitable. If this does not relieve the pain sufficiently, it is important to switch quickly to more potent drugs such as opioids and to add coanalgesics such as tricyclic antidepressants or anti-epileptic drugs.

 

Early pain relief seems to have a beneficial effect on preventing post-therapeutic neuralgia (PHN), but this has not been proven with certainty. The PHN is part of the zoster-associated pain conditions and, by definition, includes all pain that persists one month after the skin lesions have healed. An established PHN that lasts for months or years often means a significant reduction in the quality of life and a psychological burden on those affected and their surroundings.

 

Post-therapeutic pain expresses itself as sharp, dull or as sensory disturbances. Inflammatory damage to the nerves and incorrect processing of the pain are assumed to be the cause. Around half of zoster patients over the age of 50 suffer from it, 20 to 30 percent of them even after a year. There is an increased risk of developing long-term pain in patients over 50 years of age, with moderate to severe pain and with localization of the zoster on the head and neck. In contrast, the severity of the skin symptoms and the immune status do not seem to have any influence. The early intake of antivirals and adequate analgesic treatment of acute pain can reduce the risk of the occurrence and duration of such painful conditions.

 

Once post-therapeutic pain has set in, therapy is difficult. There is no first-line therapy, the treatment must be adapted to the individual response. If the response is inadequate, patients should turn to specialized pain clinics.

 

Depending on the severity of the pain, the Dermatological Infectiology Working Group of the German Dermatological Society recommends various drugs and measures individually or in combination. Based on the WHO level scheme for pain treatment, initially non-steroidal analgesics and anti-inflammatory drugs such as paracetamol and ibuprofen are used; if the response is inadequate, weakly effective opioid analgesics such as tramadol or codeine follow. In the third stage, a highly effective opioid such as buprenorphine or morphine is indicated in addition to the "peripheral" analgesic. In the case of pronounced neuralgic pain, an anticonvulsant such as carbamazepine or gabapentin can be added at an early stage. Older people in particular also benefit from antidepressants such as clomipramine or neuroleptics such as levomepromazine.

 

Finally, there are a number of other measures such as topical capsaicin therapy, external products containing lidocaine, transcutaneous electrical nerve stimulation, acupuncture or physical methods such as sympathetic blockade. Capsicain preparations should be applied carefully and must not come into contact with the eyes. After using it, you have to wash your hands very well. The treatment can lead to painful skin reactions in the first two weeks of use.

 

Vaccination prophylaxis being tested

 

Cellular immunity to VZV decreases with age and the incidence of herpes zoster diseases increases. A vaccine that boosts the cellular immune response could help protect against the disease. Based on this consideration, a herpes zoster vaccine was developed. Like the vaccine against chickenpox, this consists of weakened varicella-zoster viruses (“OKA / Merck” strain), but is 14 times as strong.

 

A randomized, placebo-controlled study with more than 38,500 people was conducted to clinically test the vaccine. The patients were over 60 years old and had developed varicella. Within three years after vaccination, half as many herpes zoster cases occurred in the vaccinated group as in the placebo group, and the incidence of PHN was around three times lower. To prevent one disease per year, 175 people must be vaccinated (number needed to treat, NNT = 175). To prevent the development of post-therapeutic neuralgia in one patient per year, 1111 people need to be vaccinated (NNT = 1111).

 

In the first 42 days, more vaccine reactions were reported in the vaccine group (erythema, swelling, pain) than in the placebo group, otherwise there were hardly any differences in terms of side effects. The zoster vaccination has been submitted for approval in the USA and Europe (proposed name: Zostavax®). The Committee for Human Medicinal Products of the European approval authority EMEA gave the Sanofi Pasteur MSD vaccine a positive rating at the end of March. As an indication, the prevention of herpes zoster and PHN can be claimed in people over 60 years of age.

 

Advice is needed

 

In young, otherwise healthy people, herpes zoster is usually an unpleasant but relatively harmless disease that can be treated symptomatically. On the other hand, people over 50 years of age, immunocompromised patients and those with an attack on the head and neck area must start systemic antiviral therapy as soon as possible, i.e. within 48 to 72 hours after the onset of the disease. This can reduce the risk of a severe course and complications. Particular attention should be paid to the adequate treatment of pain, since severe pain is a risk factor for post-therapeutic neuralgia.

 

Pharmacists can make an important contribution to the control of the disease and the quality of life of herpes zoster patients with their advice to consult the family doctor, ophthalmologist or dermatologist quickly in case of suspicion, as well as with supportive advice on pain relief.