Are your shingles skills in shambles? Shed your shame and savor the smörgåsbord of shingles science in this special show.
Shaken by a shortage of shingles savvy? Vexed by varicella-zoster imposters? Perplexed by post-herpetic neuralgia? Get ready to sharpen your expertise in varicella vaccines, learn how to tell a zoster from a zebra, and administer infection interventions with an eye towards prevention. We are joined today by special guest and returning Curbsiders expert, Dr. Boghuma Kabisen Titanji MD, M.Sc., DTM&H, PhD. (@Boghuma on Twitter!).
First Kashlak case: Diagnosis of varicella-zoster virus (VZV, aka shingles)
Mimics and atypical presentations
Treatment for uncomplicated shingles cases
Second Kashlak case: Post-herpetic neuralgia (PHN)
PHN treatment options
Management of complicated shingles cases
VZV prophylaxis and infection control
Third Kashlak case: Immunization guidelines for older adults
VZV vaccine efficacy, live attenuated vs. recombinant vaccine
Varicella (chickenpox) vaccine guidelines
Final pearls and Outro
VZV is everywhere. You are going to encounter it in your practice either as chickenpox or shingles, and it is important to recognize that both syndromes are caused by the same virus.
Shingles is a clinical diagnosis. Testing can help with atypical presentations. Tzanck smear is quick, non-specific. PCR is quick, sensitive and specific.
Transmission is both by direct contact with lesions and airborne virus (especially in disseminated disease, but has been reported in localized disease (Saidel-Odes, 2010, Bloch, 2012)! Both airborne and droplet precautions are reasonable even for hospitalized patients even with localized disease.
Dr. Titanji says it’s appropriate to start antiviral therapy as long as there are still active lesions! So go by the presence of lesions and not the 72-hour cutoff.
Identify cases that are severe and require urgent medical attention (e.g. disseminated zoster, zoster ophthalmicus, Ramsay Hunt syndrome, encephalitis) and that would benefit from early antiviral IV tx.
Vaccines work! We have effective vaccines to prevent chickenpox (LA varicella) and shingles (recombinant ZV). Advocate for your patients to make sure they are immunized.
Shingles (varicella-zoster virus): Show Notes
Shingles Diagnosis Pearls
varicella-zoster virus (VZV) is a herpes virus. Humans are only known reservoir
Two types of clinical presentation: primary infection with chickenpox → virus then becomes latent in the dorsal ganglia of spinal or peripheral nerves and can be reactivated later in life and cause a localized dermatomal rash called shingles
More than 90% of adults are seropositive for chickenpox (Reynolds, 2010) so if an adult presents with VZV symptoms it is unlikely they are presenting w/ primary infection and more likely to be a reactivation (shingles)
Shingles is a clinical diagnosis based on patient history and clinical exam, and should be guided by the appearance of the rash. A key characteristic of shingles rash is localization to a single dermatome, or at most 2 adjacent dermatomes.
Prodromal symptoms are experienced by 70-80% of patients (Dworkin, 2007) and include pain and a tingling localized to a dermatome
Rash presents initially as an eruption of macules and papules, within a few days it turns into translucent vesicles and/or pustules which crust and scab over before the rash heals
Shingles can present atypically. In cases where clinical diagnosis is uncertain, diagnostic tools to confirm VZV include:
The Tzanck smear (a direct fluorescent antibody test) analyzes a swab of the patient’s active lesions. The test is quick and can identify whether the lesion is one of 3 herpes viruses (HSV-1, HSV-2, or VZV). However, it is only 50% sensitive, will just narrow down the differential to a herpes virus, and the swab must sample active lesions (ones that have not scabbed over).
A PCR test is more expensive but also more sensitive/specific, with results turned around within 24 hours. The test looks for viral RNA and is most accurate when the sample is swabbed from an active lesion. Blood and CSF samples may also be tested, with the caveat that there may not be enough circulating viral load to be detectable.
Virus culture is a third option. It is slow to result and less sensitive than PCR testing.
Younger patients presenting with shingles should be screened for any condition causing a decline in T cell immunity e.g. HIV infection. However, any major stressor such as pregnancy, childbirth, surgery or acute illness can potentially decrease the control of viral latency by the T-cells and lead to VZV reactivation.
Shingles Treatment Pearls
Antiviral treatments can make lesions heal faster and decrease the amount of virus shedding from active lesions (which might decrease transmission). Unfortunately, no acute HZ treatments seem to reduce the chance of postherpetic neuralgia (Dynamed PHN, 2021).
It’s appropriate to start antiviral therapy as long as there are still active lesions! So go by the presence of lesions and not the 72-hour cutoff (expert opinion). To identify active lesions, look for the presence of macules, papules and vesicles. If the lesions are completely scabbed over and dried, there is no active viral shedding.
For an uncomplicated infection that can be treated at home, treatment duration should be 7-10 days and can utilize one of the following antiviral agents:
Acyclovir (800 mg 5x day); however it can be difficult for a patient to take a medication 5 times per day so the below options should also be considered:
Valacyclovir (1 g TID)
Famciclovir (500 mg TID).
Acyclovir has poor oral absorption, while valacyclovir and famciclovir have better oral bioavailability. However, there is not much research on treating nursing/postpartum patients with valacyclovir and famciclovir so if a patient is pregnant or breastfeeding, acyclovir is preferable.
Steroids: a meta-analysis (by Han, 2012 from Cochrane) found no added benefit of adding steroids for the prevention of PHN. Steroids are unnecessary unless patient has specific complication for which steroids would be indicated (i.e. inflammatory ophthalmic complications) —Dynamed HZ, 2021.
Since majority of shingles patients are 60+ years of age, important to consider whether steroids would be contraindicated due to presence of a comorbid condition
Complications & Hospitalization Pearls
Conditions that necessitate admission:
If patient is immunocompromised (e.g. renal transplant), they should be admitted and appropriate specialists consulted as these patients are at higher risk of developing multidermatomal herpes zoster (severe disease). Immunocompromised patients are more likely to experience constitutional symptoms, and higher rates of visceral complications (e.g. pneumonia, hepatitis, meningitis, encephalitis, and pneumonitis) (Denny, 2018).
Patients admitted with shingles infection will likely require intravenous antiviral treatment. IV acyclovir should be administered at 10mg/kg every 8 hours until lesions have resolved i.e. no new vesicles appearing in other dermatomes. Dr Titanji also states that pneumonitis should not be treated with steroids.
Zoster ophthalmicus is a serious sight-threatening condition. Look for vesicles around the tip of the patient’s nose! This implicates the ophthalmic branch of the trigeminal nerve. Get Ophthalmology involved and treat patient with IV acyclovir until lesions are healing, then transition patient to oral antiviral e.g. valacyclovir 1 g every 8 hours for 7 days after IV antivirals are completed. Keratitis and iritis can be complications and require topical steroids.
Acute retinal necrosis is a life-threatening complication of VZV reactivation, seen frequently in HIV+ immunocompromised patients w/ advanced disease. Symptoms include decreased visual acuity and unilateral ocular pain. This is an emergency and requires immediate attention from an ophthalmologist, who may recommend injection of intraocular antivirals as well as systemic antivirals. Expert opinion is to give IV antiviral Rx for 2 weeks in hospital then taper w/ oral antivirals up to 6 weeks (There are no randomized trials for this treatment as yet). Differential diagnosis in AIDS is CMV retinitis, but CMV retinitis is usually painless. If painful and patient is immunocompromised then call the ophthalmologist!
Ramsay-Hunt syndrome typically presents as ipsilateral facial paralysis more profound than Bell’s palsy along with vesicles in auditory canal, and unilateral ear pain. This is due to reactivation of VZV in the geniculate nucleus extending to cranial nerve VII and VIII. Get ENT involved if Ramsay-Hunt suspected. Steroids + antivirals may be indicated to help improve recovery.
Post-herpetic Neuralgia (PHN) Pearls
PHN is pain that persists for 3 months+ after the rash has fully healed, and is characterized by a sensation of burning pain in the dermatome where the shingles rash was. Other symptoms include itching, numbness, tingling, and altered sensation in the area.
Diagnosis is clinical–look for a patient with a recently resolved shingles eruption presenting 3+ months after initial infection with persistent pain
Treatment for PHN
Gabapentinoids (gabapentin, pregabalin): both medications should be slowly titrated up, and dosed based on renal function.
Gabapentin: start w/ 300 mg first day, increase to 300 mg BID on second day, then 300 mg TID by third day, can go up to 3600 mg total/day. Patients usually have a good response around 300 mg TID (expert opinion).
Pregabalin: start with 50 mg TID (total daily dose of 150 mg), can go up to a max dose of 300 mg daily (100m TID). Patients usually have a good response around 150 mg daily.
Tricyclic antidepressant medications (e.g. amitriptyline) can be used but be cautious prescribing to elderly patients who may have comorbid conditions or are more susceptible to falls, sundowning, etc.
For patients who have dementia or are at elevated fall risk, consider topical therapies like lidocaine, capsaicin cream (not well tolerated by many patients bc can cause initial burning).
Opioids may be appropriate at lower doses but there is risk of dependency.
In acute phase of shingles reaction, NSAIDs can be effective at managing pain of inflammatory neuritis. However, PHN is a longer-term neuropathic pain that will not respond as well to NSAIDs.
If still no relief, refer patient to pain specialist for additional options.
Prevention & Prophylaxis Pearls
If a patient presenting with shingles is currently nursing, it can be expected that some maternal antibodies to VZV are passed to the baby, since the patient must have previously been infected with chickenpox (Ranjan, 2020). However, if the patient has a primary infection of chickenpox the infant is in more danger because it has no immunity to infection.
Get pediatrics team involved to protect infant from potential exposure/transmission.
Covering the shingles rash can help limit transmission to others in the patient’s household.
VZV transmits via airborne droplets and through direct contact. For active vesicular lesions Dr. Titanji recommends airborne and contact precautions (PPE) since transmission has been described even with localized HZ (Saidel-Odes, 2010, Bloch, 2012)!
If an adult who never had chickenpox and did not receive the varicella vaccine is exposed to VZV, they can become seriously ill, especially if they are immunocompromised.
VZV prophylaxis may prevent infection or decrease severity of infection:
For immunocompetent patients, offer the live attenuated varicella vaccine within 5 days of exposure (2-dose series, doses given 4-8 weeks apart). For Pediatric patients, vaccines are available as a combination MMR+VZV, or as a single VZV vaccine.
NB: Live attenuated vaccine is susceptible to antiviral drugs, so do not combine antiviral or VZIG/IVIG prophylaxis with administration of the live attenuated vaccine! Start the varicella vaccine series no earlier than one month after antiviral tx is completed, and no earlier than 5 months after VZIG or IVIG infusion.
Immunocompromised patients may be a candidate for VZV immunoglobulin infusions (VZIG) or intravenous immunoglobulins (IVIG). VZIG is just concentrated and isolated immunoglobulins specific to varicella-zoster. IVIG has an array of immunoglobulins including varicella antibodies.
Dosing: Give infusion ASAP (ideally within 48-96 hours) and within 10 days of exposure (Lexicomp).
For VZIG, an adult patient over 40 kg should be given 625 units as a single infusion.
For IVIG, provide 400 mg/kg in a single infusion.
In cases of post-exposure in susceptible patients when there is no access to vaccines or immunoglobulins, antiviral medications may also be used, starting 7 days after exposure and treat for one week (expert opinion) with acyclovir, valacyclovir, or famciclovir (follow same dosing regimen as when treating an active shingles infection).
Chickenpox vaccination was added to the routine childhood vaccination schedule in the USA in 1995, but was available in some areas as early as 1988.
If patient was born outside of the U.S. and has no record of varicella vaccination status, it may be appropriate to check varicella antibody levels prior to commencing vaccination. The recombinant shingles vaccination is not used for primary prevention of VZV infection in children or those with no record of infection. Patients aged 50+ should get the recombinant VZV (shingles) vaccine. Older patients are more susceptible to VZV reactivation due to a decline in T cell immunity over time.
There are two types of shingles vaccine. The most recent to be licensed in the U.S. is the 2-dose recombinant vaccine, but there is a single-dose live attenuated vaccine phased out since November 2020 (Zostavax) .
The live attenuated vaccine is less effective. It reduces shingles by 51% and PHN by 67% if patient <70 years old, but efficacy decreases if patient is 70+ and the immunity it confers wanes after about 5 years (Centers for Disease Control and Prevention, 2020). It is not recommended for patients who are immunocompromised.
Patients previously given the live attenuated vaccine should be offered revaccination with the recombinant vaccine (Dooling et al, 2018). If patient had shingles, you can offer the recombinant VZV vaccine when the lesions are healed.
Contraindications to live attenuated vaccine include HIV/AIDS, immunocompromised patients, those with active cancer receiving chemotherapy, pregnant women
The above group of patients can be offered the recombinant vaccine.
Can VZV vaccination reactivate and cause shingles or chickenpox? Yes, but it is rare
Listeners will understand varicella-zoster virus immunization recommendations, and will learn how to diagnose and treat shingles infection, including potential complications such as post-herpetic neuralgia (PHN).
After listening to this episode listeners will…
Know that the varicella-zoster virus (VZV) causes both chickenpox and shingles, and that infection with chickenpox must occur for shingles to later develop
Review guidelines and considerations for immunizing patients eligible for the chickenpox or shingles vaccines.
Identify risk factors for shingles/severe cases of shingles
Learn the essentials of diagnosing shingles including how to differentiate its symptoms and presentation from mimics (e.g. chickenpox, herpes simplex, atopic dermatitis, psoriasis, allergic rash, contact dermatitis, etc.)
Understand the function and utility of laboratory tests to confirm a shingles diagnosis, including serologic assays and PCR/genotype testing
Recognize how VZV can be spread through contact with the shingles virus, and how to decrease risk of transmission
Be prepared to recommend treatment regimens including antiviral medications and topical treatments
Manage post-infection shingles-specific illnesses including zoster ophthalmicus and disseminated shingles
Describe the etiology of postherpetic neuralgia (PHN) and recognize its presentation in patients
Discuss treatment strategies for PHN and when to involve a specialist in patient care (and what type of specialist)
Dr. Titanji reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Watto MF, Titanji B, Roberts SP, Williams PN, Grant K. “#286 Mingle with Shingles featuring Dr. Boghuma Titanji.”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date July 26, 2021.