What Are the First Signs of Monkeypox? Here's When Symptoms Typically Show Up

Monkeypox is a disease characterized by pocks, or pustules, that show up on the skin as a result of infection. But those rashes or lesions aren't the only signs of illness—or even the first ones.

As is the case with any transmissible disease, catching monkeypox in its early stages can lessen the possibility of passing it to others. And with cases in the U.S. steeply rising in recent weeks, it's more important than ever to identify infections early so people can isolate and help curb the ongoing spread.

Here's what to know about the general timeline of a typical monkeypox infection, how the current outbreak might look different, and the prevention methods and treatments available during each stage.

Beginning Stages of Monkeypox: From First Exposure to Mild Illness

A monkeypox infection may begin much sooner than the infected person realizes, according to Sarah Waldman, MD, an associate professor in infectious disease at the University of California, Davis Medical Center.

This time period—from when a virus enters the body to the time you start showing symptoms—is known as a virus' incubation period. For some viruses, like the flu or the Omicron variant of COVID-19, it takes an average of two or three days, respectively, for the virus to incubate.

The incubation period of monkeypox, both historically and in the current outbreak, is longer than that.

Traditionally, monkeypox's incubation period is thought to be between six and 13 days, and sometimes up to 21 days, according to the World Health Organization (WHO). But data from the current outbreak suggests the incubation period of this version of monkeypox is shorter.

Dr. Waldman points to a study published in July that suggests an average incubation period of seven days—though researchers still saw a range of three to 20 days. "During this time period, someone exposed to monkeypox would not know they're sick," said Dr. Waldman.

Even when a person with monkeypox starts to show signs of infection, it won't be the telltale lesions or rashes that the disease is known for. A majority of people—about 60%, according to Dr. Waldman—will experience some kind of cold or flu-like symptoms at first.

"The first thing that usually happens [when] you get an illness—and it can vary in severity—but you can frequently have fever, some aches and pains, you're not feeling very well, you may kind of lose your appetite a little bit," William Schaffner, MD professor of infectious disease at the Vanderbilt University Medical Center told Health. "In other words, you just feel generally ill."

The Centers for Disease Control and Prevention (CDC) lists other common symptoms of monkeypox, like swollen lymph nodes and respiratory symptoms (sore throat, nasal congestion, and cough).

Although people can experience monkeypox differently, those flu-like symptoms will go away in a few days for most people, Dr. Schaffner said. And as they do, people will likely begin to see rashes or lesions popping up.

However, the CDC also points out that some people may end up getting a rash or lesions first, followed by other symptoms; and still others may only experience a rash.

Monkeypox Lesions, Stage-By-Stage

Over the course of the two to four weeks following that initial incubation period, a person infected with monkeypox will see lesions forming on the body that go through specific phases.

The enanthem stage, the Centers for Disease Control and Prevention (CDC) said, can signify the beginning of an infection in some people. Those first lesions form on the tongue or in the mouth. Not every monkeypox infection includes this stage, however.

The first stage for all monkeypox lesions on the body is called the macular stage. Bumps on the body are newly formed, and are reddened or discolored and flat against the skin. After that they'll become slightly raised—this is called the papular stage.

Once the lesions are raised, they'll fill with clear fluid and become blister-like, known as the vesicular stage.

"They're not the sort of thin blister you get from a scrape on your skin, or from chickenpox," Dr. Schaffner said. "These are what we call deep-seated. They're quite firm. One of the ways to describe them is rubbery. I mean, they push back on you, it's not as though they break easily—they don't."

The clear liquid inside the lesions will then turn opaque or yellowish, Dr. Schaffner added, and then will develop a deep depression in the center, which experts call umbilication. This is the pustule stage.

The infection begins to resolve as soon as the pustules start to turn into scabs. This process can take a couple of weeks, but eventually new, healthy skin will grow underneath where the blister was and the scab will fall off. At this point, the monkeypox infection is over.

People are most at risk of transmitting the virus during these weeks when they have lesions—this can happen through skin-to-skin contact with another person, or if someone uses and infects an object, fabric, or surface that can pass the virus along to someone else.

Experts don't yet know if any one stage is more infectious than the others, Dr. Waldman said, so taking precautions to isolate while those lesions are present is crucial.

Cases Straying from the Norm in this Current Outbreak

Although the timeline for a typical infection is pretty clearly defined, cases from this current outbreak "didn't read the textbook," Dr. Schaffner said.

"During the current outbreak, the skin lesions are following different paths," Dr. Waldman explained. "Some skin lesions are staying present for long periods of time and are challenging to heal. And other skin lesions are present for a few days and then resolve very easily."

Not only might a person see lesions in multiple different stages at once, but the number of sores and their location are also straying from what experts have traditionally known about monkeypox's presentation.

"Classically, you get quite a few rash spots, and they are visible because they're on the face and head, on the arms, on the palms, and on the legs and the feet," Dr. Schaffner said. "However, this virus in the United States often produces relatively few lesions. They can be hidden by the clothing, they can be on your trunk, and they're frequently on the genitalia or on your buttocks, around your anus."

Lesions also tend to show up in the areas where a person first came into contact with a monkeypox sore, Dr. Waldman said, and only in some cases does it spread around to other parts of the body.

Besides just changing what doctors and the general public should look out for when checking for a monkeypox infection, these variations in the current outbreak also mean that the general pain scale associated with monkeypox has also deviated from the norm.

Generally, Dr. Waldman explained, the monkeypox lesions are quite painful in earlier stages, but become less so as they scab and heal. But having lesions in such sensitive areas—in some cases even inside the mouth or in the rectum, Dr. Scaffner said—can be especially painful.

Getting the Timing Right for Treatment

Managing and treating the virus will depend on where an infected person is at in their infection, as well as their medical history and where the lesions are.

For those with especially sensitive lesions, patients can talk to their doctor about how to best manage the pain, whether that be something over-the-counter, like Tylenol, or stronger prescription pain medication, Dr. Schaffner said.

If a person is immunocompromised or is struggling with a severe, widespread infection, Dr. Waldman added, they may need to seek an antiviral treatment.

The antiviral drug currently being used to treat monkeypox, called TPOXX or tecovirimat, isn't yet approved by the Food and Drug Administration (FDA) for use in monkeypox (its FDA-approval is for smallpox). So, TPOXX has to be specially requested through a state or territorial health department, or the CDC itself.

"[The FDA has] reduced the amount of paperwork necessary, but there's still a fair amount of discussion in the medical community that they could have done and could still do more to make this drug more readily available," Dr. Schaffner said. "It's still a cumbersome process."

Besides waiting to treat an infection that's already underway, the other option is, of course, to try and prevent monkeypox sores from forming with a vaccine after exposure, or post-exposure prophylaxis.

The ACAM2000 and the JYNNEOS vaccines, which were initially created to prevent smallpox, are now being authorized by the CDC for treatment against monkeypox. In addition to high demand for vaccines outpacing supply, timing that vaccine after an exposure is also a hurdle.

"It is a small window and it's usually thought to be shorter than a week…about three [or] four days. That would be the best time to receive the vaccine to get the effect," Dr. Schaffner said.

The first dose can provide short term protection against the virus—as in, after a recent exposure. But for long standing protection, a second dose is necessary, Dr. Schaffner said. As more vaccines become available, people should be able to get the vaccine rapidly to deter an infection in the days after they believe they may have been exposed, as well as get that longer term protection.

"Stick with us, because we would like to vaccinate as many people absolutely as quickly as possible. And the more vaccine that comes in, the more broadly we can make it available," Dr. Schaffner said. "But those criteria will change over time. So hang in there."