Shingles

• 1. A Belt of Pain

  ›

  Shingles gets its everyday name from cingulus, a Latin word for a girdle. The name fits. The rash typically forms a stripe or belt on one side of the body and stops at the midline. About a third of people develop the disease at some point in their lives. The virus behind it has usually been inside them since childhood, silent and unseen. Where does it hide for decades? What wakes it? And why did doctors fear that vaccinating children against chickenpox might make shingles more common among their elders?

  38459495

• 2. Anatomy of an Outbreak

  ›

  Two to four days before any rash appears, a patch of skin may begin to tingle or ache. Fever, headache and tiredness often arrive alongside it. These early signs are so vague that they can lead to a wrong diagnosis. Next come burning, itching, oversensitivity or a pins-and-needles feeling. Pain can range from mild to severe. Patients describe it as stinging, aching, numbing or throbbing, sometimes broken by quick stabs of agonizing pain.

  In most cases the rash follows after one to two days, though the wait can stretch to three weeks. At first it looks like hives. Unlike hives, the skin changes stay inside a single dermatome, the strip of skin served by one nerve. That is why the pattern forms a belt on one side of the body. It usually appears on the torso, but it can also reach the face, the eyes or other areas.

  The rash soon turns into small blisters filled with clear fluid. They later grow cloudy or dark as they fill with blood, then crust over within seven to ten days. Usually the crusts fall away and the skin heals. After severe blistering, scars and discolored skin can remain. Most outbreaks fade within a few weeks. Some people are left with nerve pain called postherpetic neuralgia, which can last for months or years.

  In children, shingles is often painless, and the disease grows more severe with age. Some adults face the opposite puzzle. In zoster sine herpete, which means zoster without herpes, a person has the full set of symptoms but never develops the rash.

  The blister fluid itself carries the virus. It can spread by contact or by inhaling droplets until the lesions crust over, which may take up to four weeks. Someone who has never had chickenpox can catch chickenpox from that fluid. That clue points to what really lies behind the disease.

  6313924

• 3. The Sleeping Virus

  ›

  The culprit is the varicella zoster virus, a double-stranded DNA virus, and most people meet it as children in the form of chickenpox. The immune system clears the virus from most places in the body. It does not clear it from all of them. Some virus stays dormant in the dorsal root ganglion beside the spinal cord, or in the trigeminal ganglion at the base of the skull.

  Shingles begins when virus particles in one single sensory ganglion switch from a latent to an active phase. They multiply inside the nerve cell bodies, then travel down the nerve fibers to the patch of skin that ganglion serves. There they cause local inflammation and blisters. The pain, both short-term and lasting, comes from inflammation of the affected nerves.

  Why the switch happens is poorly understood. A healthy immune system normally holds the virus down. Shingles becomes more likely when immunity is weakened by aging, immunosuppressive therapy, psychological stress or other factors. Catching chickenpox before the age of 18 months is another known risk factor.

  The problem is hard to study. Researchers rely on small-animal models, and no method exists to find dormant virus in the ganglia of living people. It has turned up in autopsies of nervous tissue. Infected cells keep making virus-specific proteins during the quiet period, so true latency has never been proven. It could instead be a chronic, low-level infection. The complete genome of the virus was published in 1986.

  Herpes simplex flares up again and again, but shingles rarely returns. Fewer than 5% of people have more than one attack, and more than three recurrences is extremely rare. The two viruses are not the same, although both belong to the alpha subfamily of herpesviruses. The family name comes from the Greek herpein, meaning "to creep", a nod to the hidden, recurring infections typical of the group.

  3639414345

• 4. Eyes, Ears, and Mouths

  ›

  Roughly 10-25% of shingles cases strike the region around the eye, a form called zoster ophthalmicus. The trigeminal nerve is the nerve most often involved, and its ophthalmic branch is the usual site. The rash can cover the forehead, the upper eyelid and the area around the eye. Complications include conjunctivitis, keratitis, uveitis and optic nerve palsies. These can leave chronic eye inflammation, vision loss and debilitating pain. A rash on the tip of the nose is a strong warning sign of eye involvement. This form should be treated early and aggressively, because it can lead to blindness.

  Shingles oticus, also called Ramsay Hunt syndrome type II, involves the ear. It is thought to occur when the virus spreads from the facial nerve to the vestibulocochlear nerve. Hearing loss and vertigo, a rotating kind of dizziness, are the result.

  When the upper or lower jaw branches of the trigeminal nerve are affected, the rash can appear inside the mouth. Blisters 1-4 mm across break down quickly into ulcers that heal in 10-14 days. The pain beforehand can feel like a toothache, which sometimes leads to unnecessary dental treatment. As on the skin, the lesions stay on one side. In rare cases the virus spreads to blood vessels and cuts off the blood supply to tissue. Rare outcomes include tooth loss, gum disease and osteonecrosis.

  In people with weakened immune function, the rash can spread widely. Doctors call it disseminated shingles when more than 20 lesions appear outside the main dermatome or the ones next to it. The virus can then reach organs such as the liver or the brain. That causes hepatitis or encephalitis, and it can make the condition potentially lethal.

  2872782926

• 5. Finding the Culprit

  ›

  The writer Aulus Cornelius Celsus, who lived from around 25 BC to 50 AD, first used the term herpes zoster. Zoster comes from the Greek zōstēr, meaning belt or girdle. For centuries, accounts of the disease failed to separate it from the blistering of smallpox, ergotism and erysipelas.

  Sorting out the confusion took a long time. In the late 18th century William Heberden found a way to tell shingles from smallpox. In the late 19th century, shingles was finally told apart from erysipelas. In 1831 Richard Bright guessed that the disease arose in the dorsal root ganglion. An 1861 paper by Felix von Bärensprung confirmed it.

  The link to chickenpox came at the start of the 20th century. Physicians noticed that shingles cases were often followed by chickenpox in younger people living in the same home. The idea gained strength when lymph from a person with shingles was shown to induce chickenpox in young volunteers. Proof arrived in 1953, when the Nobel laureate Thomas Huckle Weller first isolated the virus in cell cultures. Some sources also credit Evelyn Nicol with the first isolation.

  Until the 1940s, doctors thought shingles was benign and its serious complications very rare. By 1942 it was clear that the disease was more serious in adults than in children and grew more frequent with age. Studies of immunosuppressed people in the 1950s showed it was not so harmless after all. That discovery started the search for treatments and preventive measures.

  3233813

• 6. Age and the Booster

  ›

  By the mid-1960s, studies had tied shingles to a gradual decline in cellular immunity in old age. In a group of 1,000 people who lived to 85, about 500 would have at least one attack. Today the US National Institutes of Health puts new cases at 1.2 to 3.4 per 1,000 person-years among healthy individuals. Among people over 65, the figure rises to 3.9 to 11.8. Incidence rates are similar worldwide. About half of US cases occur in people aged 50 or older. Shingles follows no season and does not come in epidemics.

  Death is very rare, at 0.28 to 0.69 deaths per million. Complications are more common. One study estimated that 26% of people with shingles eventually develop them, and about 20% develop postherpetic neuralgia. A study of 1994 California data found hospitalization at 2.1 per 100,000 person-years, rising to 9.3 for those aged 60 and up. An earlier Connecticut study found a higher rate. The gap may reflect HIV in that population, or the arrival of antivirals in California before 1994.

  Other risk factors include immunosuppression and psychological stress. A study in North Carolina reported that "black subjects were significantly less likely to develop zoster than were white subjects." Evidence for a genetic link is weak. A 2008 study found that people with close relatives who had shingles were twice as likely to get it, but a 2010 study found no such link.

  In his 1965 paper, Hope-Simpson proposed that the "peculiar age distribution of zoster" might partly reflect how often each age group meets chickenpox. Each encounter boosts a person's antibody protection and postpones an attack. A study by Thomas and colleagues found lower shingles rates in households with children. Terada and colleagues found that pediatricians had rates one-half to one-eighth those of their age group.

  That raised a worry when the United States began routine chickenpox vaccination in 1995. Older adults would lose their natural boosts. Early studies showed no consistent rise, but those studies came from places where vaccination was not yet widespread. A later study by Patel and colleagues linked the vaccine to more than $700 million a year in added hospitalization costs for shingles complications in people over 60. Yih and colleagues reported a 90% rise in adult shingles as child coverage grew. Yawn and colleagues found a 28% increase from 1996 to 2001. Wide adoption of zoster vaccination, on the other hand, could dramatically reduce the incidence.

  2345949697

• 7. Vaccines and Treatment

  ›

  Two shingles vaccines exist for people who have already had chickenpox. Zostavax is a live attenuated virus vaccine, and Shingrix is an adjuvanted subunit vaccine. Doctors recommend against the live vaccine for people with primary or acquired immunodeficiency. A Cochrane review found that Zostavax prevented shingles for at least three years, a relative risk reduction of about 50%. Among vaccinated people who still got shingles, it cut persistent severe pain by 66%. Protection held through four years of follow-up.

  Shingrix is given in two doses and provides about 90% protection at 3.5 years. As of 2016 it had been studied only in people with intact immune systems, yet it appears effective in the very old. In the United States, healthy adults aged 50 and over are advised to take two doses, two to six months apart. The UK National Health Service offers vaccination to everyone aged 70 and over, but not past 80, because it "seems to be less effective in this age group". By August 2017, just under half of eligible 70-78 year olds had been vaccinated. For children, the varicella vaccine lowers later shingles risk if given before they catch chickenpox.

  Once shingles arrives, speed matters. Antivirals such as aciclovir can reduce severity and duration if started within 72 hours of the rash. The newer drugs valaciclovir and famciclovir work as well or better. Intravenous aciclovir may help people with weakened immunity. None of these drugs, and no corticosteroid, clearly prevents postherpetic neuralgia.

  Pain relief comes in layers. Over-the-counter painkillers handle mild to moderate pain, and calamine lotion can soothe the blisters. Severe pain may call for an opioid such as morphine. After the lesions crust over, capsaicin cream called Zostrix can be applied. Topical lidocaine and nerve blocks may also help. Gabapentin alongside antivirals may ease postherpetic neuralgia.

  Even without treatment, the outlook for lasting pain can be good. In one study of untreated shingles, 85% of people over 70 were free from pain a year after the outbreak.

  512596056

• 8. Diagnosis and Hidden Cases

  ›

  Once the rash appears, a doctor can usually diagnose shingles by looking at it, because very few diseases produce a rash in a dermatomal pattern. Herpes simplex can occasionally do so, in a form called zosteriform herpes simplex. Impetigo, dermatitis herpetiformis, contact dermatitis, candidiasis, certain drugs and insect bites can also be mistaken for shingles. Diagnosis is hard before the rash appears, after it fades, or in zoster sine herpete.

  Laboratory tests help. The most popular one looks in the blood for VZV-specific IgM antibody, which appears only during chickenpox or shingles. In larger laboratories, fluid from a blister can be tested by polymerase chain reaction, or PCR, for viral DNA. Doctors now consider PCR the most reliable method, and real-time versions are rapid and less prone to contamination.

  PCR has also changed what doctors know about the nervous system. Until the mid-1990s, infections of the central nervous system caused by this virus were regarded as rare. Since 2000, wider use of PCR has made diagnoses climb. Studies found that a rash was present in only 45% of cases. Scans were usually normal, and an expected sign in spinal fluid was missing in half of a group diagnosed with VZV encephalitis.

  Meningoencephalitis caused by this virus is now recognized as a predominant cause among immunocompetent adults outside epidemics. Before PCR, many such cases were found only at autopsy or by brain biopsy, which is reserved for serious cases. Knowledge of these conditions was therefore limited to the most severe examples. DNA techniques now reveal milder cases, with fever, headache and altered mental status, and mortality in treated people is decreasing.

  152333249