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    Home > Active Ingredient News > Immunology News > For every hour of delay, the pain gets worse!

    For every hour of delay, the pain gets worse!

    • Last Update: 2021-03-23
    • Source: Internet
    • Author: User
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    *It is only for medical professionals to read for reference.
    It is said that it hurts to death~ Shingles is one of the common complications of rheumatism and immune disease, and it is the famous "Mending Sword Emperor" when the condition gets worse.

    The pain of herpes zoster is a kind of nerve pain, and the pain is often described as knife-cutting, burning, electric shock, acupuncture, or shooting.

    Post-herpetic neuralgia can last for several years, leaving scars and pigmentation, which can seriously affect the quality of life of patients and cause them to suffer great pain.

     At present, the clinical understanding of the treatment of herpes zoster is insufficient, so that patients have poor pain control during the acute stage of herpes zoster, and the incidence of sequelae pain remains high.

    We can't help asking, what else can we do to minimize the risk of morbidity and minimize the probability of sequelae of shingles in addition to the classic treatment plan? This article is divided into two parts.
    The first part discusses the treatment points with everyone, and the second part explains the infection and prevention of shingles, including vaccination options.

     01Not enough local treatment! Systemic antiviral therapy should be used before the onset of rash: Identify prodromal pain.
    Some people have local pain before the onset of herpes.

    This pain can be tingling or electric shock-like pain, or it can be burning-like pain.

    A small number of patients may be accompanied by itching and dullness.

    Prodromal pain can appear many days before the rash, and can be misdiagnosed as myocardial infarction, biliary or renal colic, duodenal ulcer, etc.

    It is often associated with abnormal sensations (such as allodynia/hyperalgesia), and it often presents as persistent pain after the rash of shingles disappears.

     Studies have shown that starting antiviral treatment for shingles before the rash has a better effect, the treatment course is shorter, and there is no sequelae of neuralgia.

    The reason may be: early diagnosis and treatment when the rash does not appear.
    At this time, the virus does not replicate and reproduce in large numbers, and the nerve damage is relatively mild.
    When the skin lesions appear, the virus has replicated in large quantities and distributed to the skin along the nerve axon.
    It is heavier.

     The skin allergy test has an auxiliary diagnostic significance for the early diagnosis of herpes zoster.

    When the patient has prodromal pain, use a cotton swab to perform bilateral skin tactile tests on the skin of the painful area.
    If there is bilateral asymmetric skin hyperalgesia or abnormal pain, it is often helpful for early diagnosis of herpes zoster.

     After the rash: early identification of the characteristic herpes zoster rash often develops quickly, and early antiviral treatment is the specific treatment for herpes zoster.

    The progression speed of shingles is measured in hours, and every 1-2 hours delay will increase the degree of future scars and pain sequelae.

     The rash of herpes zoster initially appears as red papules (Figure 1), and then rapidly progresses (within a few hours or within 1 to 2 days) into patches of small herpes or bullae (Figure 2).

    Small vesicular lesions can become more pustular within 3 to 4 days, usually on one side of the body, but in the midline, there may be a little "press line" in severe cases (Figure 3).

    After that, the damaged skin eroded and began to get better in about 10 to 14 days, leaving scars and hyperpigmentation.

    Figure 1: The rash of herpes zoster initially appears as red papules.
    Figure 2: The rapid progression (within a few hours or within 1 to 2 days) is a patch of small herpes or bullae.
    Figure 3: The small herpes lesions can be 3-4 It becomes more pustular within a day, usually on one side of the body.
    In severe cases, the line can be pressed and cross the midline of the trunk.
    Rarely, the standard antiviral treatment plan: start the system (non-local) antiviral therapy in antiviral drugs, There are currently three systemic antiviral drugs that can be used in the treatment of shingles: acyclovir, valacyclovir and famciclovir.

     Among them, acyclovir can be administered both orally and intravenously.

    Various guidelines for the dosage of oral acyclovir are controversial.

    The Chinese guidelines for the treatment of herpes zoster recommends the oral administration of acyclovir as follows: 5 times a day, 400 mg each time, for 7 days.

    The domestic aciclovir tablets instructions and usage: 200~800mg once, five times a day.

    The guidelines of some European and American countries recommend oral administration of acyclovir as follows: 5 times a day, 800 mg each time, for 7 days.

     The clearance of acyclovir and its analogues depends on renal function, so it is necessary to adjust the dose in the case of moderate to severe renal insufficiency.

    Some studies believe that high-dose acyclovir can prevent the occurrence of drug-resistant strains and increase the efficacy.

    Although the dose for the treatment of herpes zoster infection is higher than the dose usually required for herpes simplex virus infection, the safety of these nucleoside analogs at the current recommended doses has been clearly demonstrated.

    For patients with rheumatism and immune diseases, we have reasons to take adequate medication when the situation permits.

     The bioavailability of oral acyclovir is not as good as that of intravenous administration.
    Intravenous administration of acyclovir is the standard treatment for immunocompromised patients with herpes zoster.
    The dose is 5-10mg/kg, intravenously, q8h.

    During the administration period, patients should be given adequate water to prevent acyclovir from precipitating in the renal tubules and causing damage to renal function.

    For patients with impaired renal function, the doses of intravenous acyclovir, oral acyclovir, valacyclovir and famciclovir should be adjusted accordingly.

     Clinically, we sometimes prefer valacyclovir or famciclovir over acyclovir, because the first two drugs require less frequent administration.

    The current research does not indicate that one drug is better than another.

     References for various treatment doses of "Lovir" for shingles are as follows: ●Valacyclovir: 1000mg, 3 times a day for 7 days; ●Famciclovir: 500mg, 3 times a day for 7 days; ●Acyclovir Wei: 800mg, 5 times a day for 7 days.

     It should be noted that although shingles is a "skin disease", systemic antiviral therapy should be initiated, not just topical acyclovir ointment.

     Immunodeficiency and virus resistance: When treating herpes zoster in immunodeficiency patients, acyclovir treatment depends on the severity and clinical manifestations of immunodeficiency.

    If the CD4 cells are roughly within the normal range (>400 cells/µl), segmental shingles can be treated with the standard dose of acyclovir (5-7.
    5mg/kg/8 hours) intravenously.

    Severe immunodeficiency with extensive skin lesions, especially when there are neurological symptoms, should be treated with high-dose acyclovir (10mg/kg/8 hours) intravenously, and renal function should be continuously monitored.

    Since acyclovir is nephrotoxic and has an accumulation effect on patients with impaired renal function, the serum creatinine clearance rate must be tested when acyclovir is given for the first time.

    In patients with reduced serum creatinine clearance, the interval between the next acyclovir infusion must be extended from 8 hours to 12 or even 24 hours.

    Intravenous acyclovir treatment usually results in clinical improvement within 48 to 72 hours.

    If the condition improves slowly or does not improve at all, it is considered acyclovir resistance.

    Foscarnet can be given intravenously, but the nephrotoxicity of foscarnet should also be noted.

     For the first visit after the appearance of skin lesions> 72 hours, should antiviral therapy be initiated? If the patient sees a doctor after more than 72 hours of skin lesions and new skin lesions still appear at the time of consultation, we will give antiviral treatment, because this indicates that the virus is still replicating.

    However, for hosts with normal immune function that have skin lesions for more than 72 hours, the clinical utility of initiating antiviral therapy is still unclear.

    For patients with skin lesions that have scabs, antiviral therapy may have little effect.

     In addition, the active period of herpes zoster virus generally does not exceed 14 days.

    After the onset of shingles, the body produces antibodies to clear the virus.

    After 14 days, even if the rash does not get better, antiviral treatment is not necessary.

     In the following cases, even if skin symptoms appear 72 hours after the initial visit, systemic antiviral therapy should be started: disseminated herpes zoster with internal organ involvement, persistent ocular herpes zoster, and ear herpes zoster, And patients with immune deficiencies.

     Therefore, all patients with rheumatoid immune disease with low immune function should start antiviral therapy after contracting shingles, even if the symptoms appear for more than 72 hours.

     Identify concurrent bacterial infections: secondary bacterial infections of shingles rashes are rare but still occur.

    If a bacterial infection is suspected at the initial evaluation, in addition to antiviral treatment, the patient should also receive appropriate antibiotic treatment with an antibacterial spectrum covering Staphylococcus and Streptococcus.

     Shingles often gets better after 10 to 14 days.

    If the skin still has erosions after 2 weeks, the secondary bacterial infection after skin erosion should be considered.

     Patients should be informed that if there is increased erythema, elevated skin temperature, or suppuration around any skin lesions, they should contact their clinicians.

    The above performance may suggest secondary bacterial skin infections.

     If shingles grows in "important areas", more active treatment is needed.
    If shingles grows in "important areas", the head and face, especially near the eyelids, or the vulva, these areas are rich in nerve endings, and long-term nerves are left behind.
    The probability of pain is higher, and the remaining scars will also affect the appearance.

    Therefore, if there is painful small herpes in "important parts", you must be extra vigilant, confirm the diagnosis as soon as possible, start antiviral treatment as soon as possible, use the maximum dose of "XX Lovir" allowed in the instructions in time, and choose intravenous as much as possible Instillation of "Acyclovir".

     Herpes involving the conjunctiva and ear canal should be treated with specialist consultation.

    Combined hormones: hormones can inhibit inflammation, speed up recovery, and reduce sequelae neuralgia.
    In the early stage of acute herpes zoster attack, hormones can inhibit the acute inflammatory process, reduce post-inflammatory fibrosis of ganglia, shorten the duration of neuralgia, and even reduce the occurrence The chance of neuralgia after shingles.

    The Chinese shingles treatment guidelines recommend that prednisone is generally used (30mg/day, the course of treatment is 7 days).

    For relatively healthy local herpes zoster patients over 50 years old, combined treatment with antiviral drugs and glucocorticoids can improve the quality of life of the patients.

     When accompanied by hypertension and diabetes, the author believes that patients whose blood pressure is less than 80/100mmHg and whose fasting blood glucose control is basically up to the standard should use corticosteroids in a timely and bold manner.

    Patients with rheumatic immunological diseases maintain the original treatment plan, and add immunomodulators such as thymosin or immunoglobulin when necessary.

    Tumor patients should postpone radiotherapy and chemotherapy.

     Treatment of neuralgia: The first choice for the treatment of neuralgia after herpes zoster is usually tricyclic antidepressants (TCA).

    Our preferred tricyclic drug for post-herpetic neuralgia is amitriptyline, the starting dose is 10 mg per night, and it is slowly increased to the effective dose under tolerable conditions, and the maximum daily dose is 150 mg.

     However, TCA increases the risk of adverse events in elderly patients, and should be used with caution in older patients, especially those with cognitive impairment or dementia.

     For patients with moderate to severe neuralgia who have contraindications or cannot tolerate TCA, we recommend gabapentin or pregabalin.

    Use gabapentin and pregabalin, while taking care of kidney function.

    For neurological patients with mild to moderate local pain, if they do not want to use tricyclic drugs, gabapentin and pregabalin for systemic treatment, we recommend topical capsaicin.

    However, topical capsaicin is often poorly tolerated and can be replaced with topical lidocaine, which can provide short-term relief.

    Opioid drugs can be abused and addicted, so many experts regard these drugs as second- or third-line treatments for herpes zoster neuralgia.

    However, if preventive drugs (tricyclic drugs, gabapentin, and pregabalin) are unsuccessful, opioids can be used with caution.

    02How to prevent shingles? Routes of infection vs.
    prevention of spreading shingles to others The first infection usually occurs in childhood and causes chickenpox.

    Patients with shingles can transmit the virus to individuals who have never had chickenpox and have not been vaccinated against chickenpox.

    The virus spreads from person to person through direct contact or aerosolization of the virus at the skin lesion.

    Compared with chickenpox, shingles is much less contagious.

     Local herpes zoster is only contagious after the rash is onset to before the skin lesions scab, is not contagious before the appearance of blisters, and disappears after the skin lesions are epithelialized.

    However, patients should be informed of the risk of spreading the virus to others.

    In addition, before the rash scabs, patients should be informed: If possible, keep the rash covered and wash your hands frequently to prevent the spread of the virus to others.

    Avoid contact with pregnant women who have never had chickenpox and have never been vaccinated against chickenpox, premature or low birth weight infants, and individuals with weakened immune functions.

    Vaccination Patients with rheumatism who are receiving immunosuppressive therapy and people over 50 years of age are recommended to be vaccinated against herpes zoster.

    For tumor/lupus patients who cannot be vaccinated, it is worth considering that family contacts of the patient are vaccinated against herpes zoster.

     There are currently two shingles vaccines: recombinant glycoprotein E vaccine (RZV); live attenuated vaccine (specifically ZVL).

    In many countries, ZVL and RZV are available.

    If you have a choice, we recommend that most people with normal immune functions receive RZV instead of ZVL, a live attenuated vaccine.

    There is evidence that RZV is more effective, so we prefer RZV, especially for people aged 60 to 90.

     RZV is currently on the market in China, and RZV is the first choice for patients with rheumatoid immune diseases and family contacts.

     Compared with RZV, ZVL has some advantages.

    For example, ZVL requires 1 dose of vaccine, while RZV requires 2 doses of vaccine.

    In addition, ZVL has fewer side effects that interfere with daily activities.

    The incidence of systemic side effects such as myalgia, fatigue, headache, chills and fever in ZVL vaccinators is usually <1%, while the incidence in RZV vaccinators is about 11%.

    But these side effects usually subside within 1 to 3 days.

     Although there are no long-term data on RZV, the follow-up for RZV prevention of shingles has been extended to 4 years; in addition, long-term follow-up found that a small number of patients have continued high levels of immune response for up to 9 years.

    It is recommended to re-vaccinate every 4 to 5 years.

    Reference materials: 1.
    Early comprehensive treatment of herpes zoster, Zheng Beijie 2.
    Talk about the "shingles" of the Department of Rheumatology and Immunology, Yang Xiuyan 3.
    Uptodate: vaccination to prevent herpes zoster; varicella-zoster virus infection causes zoster Herpes 4.
    The Chinese shingles treatment guidelines, the expert group of the "Chinese shingles treatment guidelines" of the Dermatologist Branch of the Chinese Medical Doctor Association
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