Herpes zoster (HZ) is a prevalent infectious and neurological entity, whose incidence has increased in the last two decades. At least 20-30% of the population and up to 50% of those over 85 years of age will be affected by HZ, although this is changing with vaccination.
Dermatologists often differ in their management approaches, and vaccination strategies for HZ are inconsistent despite various recommendations. Furthermore, infection control policies in healthcare settings for patients and staff with or exposed to HZ are often misunderstood, outdated, or poorly described in institutional guidelines.
A pathological entity with such disparate management strategies must be clarified. This case-based review aims to illustrate the management and education of patients with HZ and their care teams.
| Cases and review |
> An otherwise healthy 72-year-old man presents with painful pink papules along the right mid-back for 3 days. He believed he had been bitten by a spider or tick and asks "how he caught it."
A substantial gap in the management of HZ lies in the use of its true pathophysiology to narrow differential diagnoses and avoid unnecessary tests, treatments, and concerns. Zoster is the Greek term for "belt" or "girdle", and "shingles" comes from the Latin cingulum meaning "to surround the body"; both exemplify the classic painful dermatomal papulovesicular thoracic distribution of more than half of HZ cases.
Varicella-zoster virus (VZV), human herpesvirus type 3, is responsible for HZ infections and primary chickenpox and is part of the α-herpesvirus subfamily with the ability to remain latent in neural tissue.
All patients with HZ have incurred some version of exposure to VZV, usually in childhood, either through contact with the disease or vaccination.
For the former, the initial infection may have manifested as diffuse, self-limiting cutaneous papulovesicles, rarely with systemic complications, or perhaps subtle findings, even poorly remembered by the patient. After 1995, the current population of children and young adults may have instead received the live attenuated VZV vaccine.
VZV may remain latent in the spinal root or cranial nerve ganglia after the original exposure. Throughout life, subclinical reactivations may occur due to community contact with the virus, increasing immunity.
For the immunocompetent, this balance is maintained into adulthood until the age of vaccination for HZ is reached or, if a threshold level of immunity is not reached, until HZ ensues. The most common contributors to this waning immunity are age, intrinsic or pharmacological immunosuppression, or the original immune protection silenced following infection or vaccination.
> 30-year-old pregnant woman (28 weeks) with a rash consistent with acute chickenpox infection with diffuse vesicles all over the body. Her daughter was born at term without complications, but at 10 months of age she developed a herpetic rash involving the T3 region.
If a woman develops chickenpox during pregnancy, technically the fetus is experiencing its first exposure to VZV at the same time.
In the first two trimesters the risk of congenital viral complications from varicella is high (~25%), including low birth rate, preterm birth, and congenital varicella syndrome, and later in pregnancy, primary maternal exposure to VZV can occur. cause neonatal chickenpox.
Furthermore, primary VZV transmission in the third trimester or primary VZV infection in the first year of life leads to an increased risk of early HZ (< 4 years of age), due to the incipient cellular and humoral immunity of the fetus and the child. infant and the silenced immune response to infection.
HZ in children can also occur due to true immunosuppression, malignancy, immunomodulatory medications (systemic corticosteroids or azathioprine), surgery, trauma, and autoimmune disorders such as lupus, rheumatoid arthritis, inflammatory bowel disease, asthma, HIV, and type 1 diabetes.
In general, cases of pediatric HZ are rare, especially after vaccination for primary VZV. The presentation is usually less symptomatic and with less risk of post-herpetic neuralgia (PHN) than in adults.
Vaccinated children are 72% to 79% less likely to develop HZ in childhood than unvaccinated children. Over time, with fewer primary wild-type VZV infections and assuming high vaccination rates in the community, vaccinated children will be adults with a reduced risk of HZ.
> A 24-year-old ill-appearing African American man presents with tense vesicles that spread rapidly over the body. He is feverish and cannot walk due to painful lesions in the plantar and genital regions. He is admitted and treated with intravenous acyclovir. The diagnosis of concurrent HIV infection is revealed.
Some presentations of HZ suggest a disseminated infection that requires, in addition to hospitalization for treatment, evaluation of immunosuppression if there are risk factors. Disseminated HZ is defined by at least 20 generalized vesicular-bullous lesions outside the primary and adjacent dermatomes, with lesions evolving 1 to 2 weeks after primary presentation. There is usually prominent pain and other systemic signs that mimic primary VZV viremia, and with increased risk of pulmonary and neurological disease and secondary complications due to bacterial infection.
Patients with HIV and hematological malignancy or immunosuppressive treatment, as well as transplant recipients, have a higher risk of dissemination and their presentations can vary or even evolve into a chronic disease.
The incidence of HZ is decreasing in HIV patients due to the evolution of antiretroviral therapy, but due to the suppression of T cells immune to VZV, it is still common and shows severe symptoms, such as genital presentation. Additionally, immunosuppressed patients may have resistance to acyclovir and experience more severe NPH, particularly when HZ occurs in the V1 dermatomal distribution.
> 83-year-old woman with rapidly evolving painful, pruritic, crusty pink papules on her right cheek. She’s not sure she remembers her medication list.
The differential diagnosis of HZ is broad depending on the symptoms, particularly if the classic dermatomal papulovesicles are not present acutely. Prodromal pain can simulate a myocardial event, stroke, pulmonary embolus, renal colic, appendicitis, cholecystitis, acute angle glaucoma, and costochondritis, among others.
Zoster sine herpete (without skin involvement) is a diagnosis of exclusion when the aforementioned conditions are part of the differential. Skin mimics of HZ include other herpetic eruptions such as herpes virus type 1 or 2 (HSV-1, HSV-2), HSV superinfection, advanced VZV after childhood vaccination, among other viral diseases.
Noninfectious etiologies include allergic contact dermatitis, arthropod attack, autoimmune blistering disease, or, as in this case, a medication reaction from use of topical 5-fluorouracil.
The clues to rule out this wide differential involve pointing out the dermatomal distribution; Although HZ may involve aberrant papules in nearby dermatomes, the shape should primarily follow a representative dermatome. Polymerase chain reaction (PCR) for VZV DNA, and direct fluorescence antibody (DFA) remain the preferred diagnostic tests when considered necessary.
> 62-year-old man with HZ in V1 treated with oral antivirals. Consult to ask if there is anything else he can do to help the HZ injuries heal faster and relieve the pain. He is a university engineering professor and has been reading about prednisone and gabapentin .
The decision of how to treat HZ can be complex. In standard cases, one week of antiviral therapy (acyclovir, valacyclovir, or famciclovir) is indicated within 72 hours of the primary rash, particularly if the patient is in significant pain, develops new skin lesions, or is at risk of complications.
Intravenous antiviral therapy (acyclovir or foscarnet) is indicated for disseminated disease, ophthalmologic involvement, severe neurological symptoms, or other toxic signs. Treatment of HZ with oral antivirals reduces the time to resolution of the lesion and viral dissemination and controls pain, but does not prevent PHN. For children at risk of complications, acyclovir is the only one approved. There is no indication for topical antiviral therapy for the management of cutaneous or mucosal HZ.
Mild cases of HZ may only require localized wound care and pain relievers such as ibuprofen or paracetamol. For more pronounced symptoms, systemic corticosteroids can reduce acute HZ pain and improve daily function; They particularly improve the quality of life of patients with severe initial pain at any site or with specific neurological or ophthalmological involvement, but do not prevent PHN.
Not only can opioids reduce severe pain, but they also do not prevent PHN. The use of neuroleptics (gabapentin) and tricyclic antidepressants (TCAs) in acute HZ pain is not supported, despite some evidence of usefulness for NPH symptoms.
The first branch of the trigeminal nerve (V1) is affected by HZ in ~10-15% of cases and may initially present as Hutchinson’s sign at the tip of the nose. Acute antiviral treatment and possible treatment with systemic corticosteroids are indicated and referral to ophthalmology is advisable to diagnose and prevent ocular complications.
> 80-year-old woman with a history of HZ 5 years ago presented to dermatology with what her doctor considered "recurrent zoster." She is disgusted and actively rubs her forehead during the consultation.
This case describes dysesthesia associated with NPH after HZ, which can be confused with chronic or recurrent HZ. NPH is defined as clinically relevant pain or altered sensation that persists in regions affected by HZ at least 3 months after the initial eruption. It may be due to a sensory nerve disruption caused by VZV replication, with inflammation and tissue damage in and around the dorsal root ganglion or cranial nerve root corresponding to the affected dermatome.
The skin may show chronic signs of trauma, bacterial superinfection and healing scarring of the HZ rash and any self-manipulation due to dysesthesia and/or pain, building the misconception that an active viral rash still remains. Symptoms may persist for more than 1 year.
The only intervention to prevent PHN is the HZ vaccine. Beyond that, there are countless strategies that can help control NPH pain, with no particular consensus on optimal agents, onset window, or dosage. Gabapentin can improve NPH but does not prevent it. It has a slow onset of action, many dosage options, and a range of adverse effects.
Some opioids and TCAs also control the pain of PHN, although gabapentin is more widely prescribed. One of these medications should be considered to decrease the intensity of NPH pain in patients at higher risk for chronic debilitating symptoms.
There is some evidence of short-term relief from topical pain relievers such as lidocaine. Referral to specialists in pain management or neurosurgery for possible interventions, such as intrathecal administration of corticosteroids, may be recommended in cases of recalcitrant PHN.
> A patient’s wife is taking adalimumab for psoriatic arthritis. Ask if she and her husband should get the "shingles vaccine." She is 52 years old and he is 61 years old. He got the "old vaccine" 2 years ago, but they ask about the new version.
Vaccination for HZ aims to provide specific cell-mediated immunity against VZV. The subcutaneous single-dose live attenuated HZ vaccine Zostavax was the first approved by the FDA in 2006 for adults ≥ 60 years of age. Zostavax reduces the healing time of acute HZ injury and the severity of symptoms if a vaccinated patient develops HZ, and its PHN prevention rate is 47.4 to 77% with consistent initial efficacy, but less preventive effect over time from application.
It has few adverse effects (local reaction, headache), but since it is a live vaccine, immunosuppressed populations may not be candidates for its use. In addition, it contains preservatives and is contraindicated in patients with anaphylaxis to neomycin or gelatin.
In 2017, Shingrix, a recombinant subunit (non-live) vaccine with adjuvant, was approved by the FDA and CDC for people ≥ 50 years of age. It is a two-dose intramuscular vaccine that must be administered 2 to 6 months apart and can be administered in patients who have already received Zostavax if they have spent at least 2 months between vaccines. No vaccine should be administered during an acute HZ outbreak or while a patient is taking antiviral medications for any indication.
The efficacy of Shingrix is higher, namely 84.7 to 97.4% prevention of HZ and 88.8 to 91.2% prevention of PHN, with less variability or decrease in efficacy with age, and with less severe presentations of HZ and PHN in cases of great progression. Its adverse effects are more pronounced (localized pain, flu-like symptoms), and the only real contraindications for its use are anaphylaxis with the first dose and acute illness.
The usefulness of this vaccine in special populations is still being studied. Those patients with chronic diseases, particularly chronic renal failure, diabetes mellitus, rheumatoid and psoriatic arthritis, and systemic lupus erythematosus, are at risk for severe cases of HZ, and although immunosuppressive medication could, in theory, mount a muted immune response to vaccine, the main benefits of HZ prevention are supporting vaccination.
> An otherwise healthy 80-year-old woman comes to the clinic because the previous week she had been treated by her doctor for HZ in her left upper arm, and, while she finishes her course of acyclovir, she wants to know if she could care for her little great-granddaughter. . She also wants to know if she could "get" HZ from the vaccine like she "got" the flu after her last flu shot.
Isolation guidelines for HZ reflect the location of the rash, age, and immune status of each patient and their contacts. In immunocompetent patients with classic presentation, standard precautions (hand hygiene and respiratory protocol) should be followed, and lesions should be protected until they are dry and crusted.
For cases with mucosal distribution, mainly trigeminal, the same guidelines apply. In this case, the standard precautions mentioned above are prudent. Since your great-granddaughter is an infant who has not received any doses of VZV vaccine, she would be at risk for VZV infection from a HZ patient who is actively shedding the virus.
However, considering that the patient is not immunocompromised and has been receiving oral antiviral treatment for one week, and that the HZ rash area is easily covered and bandaged, the risk of VZV transmission is negligible. On the contrary, in immunosuppressed people, VZV can be eliminated more easily, and perhaps for prolonged periods.
Patients often ask about the infectivity of the HZ vaccine itself. With Zostavax, within a 42-day window, “zosteriform” rashes have been reported at non-injection sites, consistent with incidental wild-type HZ. There are isolated cases of Zostavax vaccine strain Oka virus as a source of HZ in immunocompetent patients, just as there are cases of pediatric Oka strain HZ from childhood vaccination for VZV, but outside the acute window of 1 to 2 months.
This occurs after the HZ strain returns to a latent state in the dorsal root or cranial nerve ganglion, and is not attributable to an acute reaction to the vaccine itself. This is debatable as the use of Shingrix exceeds that of Zostavax, and a recombinant vaccine does not undergo latency or reactivation as a live vaccine would.
> Healthy 32-year-old pregnant woman (32 weeks, first pregnancy) who notices "tearing" pain on the right side of the abdomen for 2 days, followed by a cluster of pink papulovesicles in that area and on the right upper back . She works in an outpatient clinic. Her sister also had a rash like this during pregnancy .
Theoretically, the immune response of a healthy pregnant woman may be less vigorous due to maternal cellular immunity shared with the fetus, therefore HZ may occur more frequently than in non-pregnant women.
Unlike the true viremia of primary VZV infection, which is now rarer in the US due to routine prenatal screening for VZV, HZ does not cause viremia with transplacental infection and acquired maternal VZV-specific protective IgG antibodies. due to vaccination or previous primary VZV infection, they pass between mother and fetus. This also, in theory, protects the neonate if the pregnant woman develops HZ around the time of delivery, but the aforementioned standard precautions and wound care would still be indicated.
In this case of a pregnant healthcare worker who develops HZ, the fear of transmission to the fetus would be allayed, as she should have undergone occupational screening for VZV immunity through documentation of childhood VZV, VZV vaccination, or laboratory immunity.
If the healthcare worker’s environment includes people who are not immune to VZV, particularly infants or immunosuppressed patients, scrupulous diligence with standard precautions would be prudent. In this case, since the HZ area is a region of the trunk that is constantly covered, if you comply with antiviral treatment in the appropriate window, the risk of viral dissemination and infection to other patients would be negligible.
Antiviral therapy for HZ in pregnancy is considered safe, and its timely initiation counteracts serious morbidity, including pain and wound complications, which could negatively affect the well-being of the fetus.
In this case, the patient’s sister had also developed HZ in pregnancy, which may reflect a strong genetic predisposition to HZ throughout maternal ancestry. This may be relevant to HZ vaccination in younger fertile populations as surveillance studies continue.
Zostavax is currently contraindicated in pregnancy. For Shingrix, there is no data that excludes pregnant women from receiving the vaccine and, in theory, its indication of age ≥ 50 years may include a minority of them. The risk of contact during breastfeeding to an infant of postpartum women receiving any of the HZ vaccines is unknown.
