What If I Have a Sudden Fever?
EVERYONE IN A CANCER CLINIC is obsessed with the idea of preventing infection. There are posters everywhere telling you to notify the receptionist if you have a fever or a cough. And you probably notice the way everyone is using the hand sanitizers mounted outside each exam room and along the hallways. There are good reasons for all of this concern. Cancer cells can invade tissues and organs in a way that makes infection more likely to develop. Chemotherapy can also affect your immune system by lowering the rate of neutrophils in your blood, which are the body’s first line of defense against infection. These cells help your body kill or neutralize the normally occurring bacteria on your skin, in your mouth and lungs, and in your digestive tract and keep them from entering your bloodstream. As your rate of neutrophils goes down, you are at increased risk of developing infection from bacteria that already exist in your system. In some cases, the port inserted to make chemotherapy infusions easier can become a site of infection. Although a developing infection is a serious condition that requires medical attention, it’s also quite common. In most cases, it is also easily treatable.
In this chapter, I’ll describe the signs of infection, how your doctor will try to discover the source of the infection, and how most infections are treated. Patients who are receiving a certain type of targeted therapy called immunotherapy are also at higher risk of developing certain types of infections, and you should know about those. I’ll also describe the process of bone marrow transplant and how this affects your likelihood of developing infection.
Signs of Infection
The most telling sign of infection is a fever. Always call your doctor if you have a fever of 100.5 degrees or higher or have shaking chills. The higher your fever, the more serious your infection can be. Most adults don’t get high fevers, even when they have the flu, and your doctor will suspect that an infection is causing your elevated temperature. While you might have the flu instead, we never assume flu if you have cancer.
If you have chills that cause you to shake, you may be starting to spike a fever. If you have shaking chills, take your temperature right away and then take it again after fifteen minutes.
Other signs of infection include the following:
New Symptoms and Infection
These are the most common signs of infection, but if you have any new symptoms, you will want to share them with your doctor. I had a patient once who had a known infection somewhere in his body because he had bacteria in the bloodstream. We did full-body CT scans but found no source. I kept asking him whether he had new symptoms of any kind, and he kept saying no. As he stood up to leave the exam room, he dropped his papers, and I noticed how gingerly he bent down to pick them up. I asked if he was in pain, and he told me that his sciatica was acting up. I asked him why he had never mentioned it, and he told me that he’d had the sciatica for years and that I’d asked for only new symptoms. Fair enough, but I went back to radiology and asked them to take a closer look at one of the tumors that had spread (metastases) to his lower spine and compare it to the previous scans. Did it look different? The radiologist thought that it did. I ordered a biopsy and sent that out for a culture, and it came back positive for bacteria. An infection had developed around the site of the tumor, and that was the cause of his infection. Two days later, a surgeon removed that abscess, and the infection was cured with the help of antibiotics.
Some people may be at higher risk for developing infection during treatment if they’ve had recurring infections in the past. Vicki had a patient who was just starting to be treated for breast cancer. She felt great during treatment and told Vicki that, aside from the infusions, she could hardly believe she had cancer. On about the ninth day after her third infusion, she told her husband she was suddenly tired and wanted a nap. An hour later, her husband found her asleep and drenched in sweat. She had a temperature of 102 degrees, which is extraordinarily high in an adult. She called the clinic and came in immediately to have her blood drawn. The attending doctor ordered antibiotics for her even before the blood work came back, and when it did come back, it indicated that she had the start of what would have been a runaway infection. Later the patient told Vicki that she’d had a history of urinary tract infections, particularly after sex. So Vicki’s sensible advice was to mark a calendar for the seventh, eighth, and ninth days after each infusion and to refrain from sex on those days because the risk of infection is greatest on these days.
Getting Treatment
Infections can be caused by three types of organisms: bacteria, fungi, and viruses. If you have a bacterial infection, which is the most common type, you’ll take antibiotics to kill the offending bacteria. Fungal infections usually occur in the setting of a leukemia or lymphoma where the immune system is altered, or when patients have had a prolonged course of steroids. Sometimes fungal infections occur in patients who are debilitated from their cancer. Antifungals do kill the fungi but can require many weeks of treatment to be effective. Viruses, such as herpes or shingles, are treated with antivirals. You may be more prone to reinfection from recurring viruses while in cancer treatment.
You might need several days or weeks of medication to control your infection. However, some patients will need to be on and off these medications indefinitely. In some cases, you will have to come into the hospital for radiation treatments or even surgery to control the infection. The good news is that most infections can be cured or controlled.
It can be tempting to dismiss a slight fever or nagging cough or the sudden onset of fatigue and chills because these seem insignificant compared to many of the other side effects of cancer treatment. It’s tempting for anyone to want to take a Tylenol, put on a sweater, or have a nap hoping to feel better in a couple of hours. But cancer is notorious for triggering infections inside the body, and even a small infection can get out of control in a hurry. You can get dangerously sick within a couple of days. If uncontrolled, you can develop sepsis, a condition in which bacteria is in your bloodstream and causes your blood pressure to drop quickly. At that point, you can die of infection. By contrast, if you call the clinic, sit through a blood test, and find out that you really do just have the flu, no one will be upset.
Can I Catch Infection?
People with cancer are always worried about whether they can catch infections from friends, family, or being out in a crowd, and sometimes they ask whether they need to wear a mask. For most patients with cancer, your ability to catch these routine viral infections is about the same as it is for those who don’t have cancer, and wearing a mask is generally not helpful. Of course, getting a cold or a flu is not fun even when you are perfectly healthy, so use good judgment in avoiding people who are already sick, and keep hand sanitizer with you while you are out and interacting with other people.
You may wonder too whether you need to take antibiotics before any dental procedures or teeth cleaning. Usually, that’s not necessary unless you have a known heart murmur and have always taken this precaution. Theoretically, any hardware inside your body (PICC line or portacath or stent; see chapter 5) can become infected after a dental procedure or cleaning. That’s why your doctor might prescribe antibiotics before a dental appointment if you have one of these devices.
Blood Tests and Infection
The main reason your medical team will be closely monitoring your blood counts during every treatment is to monitor your risk of infection. Your level of white blood cells will decrease in the days following each infusion, and you should know that you are more prone to infection about seven to ten days after an infusion, when your white blood count will be lowest.
Whenever your doctor orders a complete blood count (CBC), you should ask him or her to check to see whether your lymphocytes are functioning normally. If they are, then your risk of infection is low because your immune system is likely healthy. If not, your doctor can talk to you about how to avoid the possibility of developing an infection after your infusion. Actually, your chemotherapy might further reduce your chance of getting an infection because it will be attacking the cancer cells that might cause infection.
You should also ask about your level of neutrophils (ANC) after every blood count. This level reveals your underlying risk of infection. Even if your level of neutrophils is high enough for you to receive your infusion, you can still be vulnerable to infection afterward. It’s good to know your ANC level, because if you call your doctor or nurse practitioner because you think you might have an infection, it’s the first question he or she will ask.
Neutropenia
There will be predictable times during the chemotherapy cycle when you are most at risk for an infection. For most regimens, this occurs seven to ten days after the chemotherapy was administered. Chemotherapy regimens that are given weekly hold a lower risk of infection because the white blood count doesn’t get that low.
Most hormonal agents (including antiestrogens such as tamoxifen and antitestosterone agents such as leuprolide [Lupron]) don’t carry a significant risk of bone marrow suppression and thus don’t carry a significant risk of infection. You can ask your oncologist whether the risk of infection for your specific treatment is low, medium, or high. For patients at high risk of infection, we will often use growth factors to spur on the bone marrow to make more white blood cells.
When your white blood count is low, you may have few overt signs of an infection. Sometimes the only sign that you have an infection is fever. This is known as febrile neutropenia. All the other signs of fever—cough, redness, swelling, or pain—are caused by the white blood cells infiltrating an area in an attempt to fight the infection. When chemotherapy lowers your white blood count, there aren’t enough cells to create these other symptoms. That’s why getting medical attention immediately is critical. Without treatment, bacteria from the infected area can get into the bloodstream, causing blood infections such as sepsis, septicemia, or bacteremia, which are medical emergencies.
Thankfully, most cases of febrile neutropenia are easily treated. In fact, a few patients come to regard infections as a routine side effect. I was recently serving as the attending doctor in the cancer ward, where I admitted a woman for her eighth episode of febrile neutropenia. She told me that she has a routine where she calls her doctor to tell him that she’s febrile again and coming into the hospital. She goes right to the infusion unit and has blood drawn and cultured. The nurses start antibiotics while she waits for a bed to open up. After two days of intravenous antibiotics, her neutrophil level is back above 1,000, and she goes home. She looks great and she told me that she feels great, but she knows she’s susceptible to bacterial infections when her blood counts get too low.
Most episodes of febrile neutropenia respond well to antibiotics. If you are at high risk for developing infection, your doctor may prescribe growth factors, which are medications that help boost your neutrophil count.
Treatments That Cause Infection
It’s possible for you to develop an infection as the result of a recent surgery. Sometimes the wounds don’t heal as they should, and an infection can develop under the tissue as it heals. In that case, you might have to go back into the hospital and have a surgeon reopen the incision to allow the pus to heal directly out of the wound. Radiation treatments can also result in chronic infections. While radiation kills the cancer cells, it can also reduce blood flow to healthy tissue, and, when the tissue doesn’t get good blood flow, it can’t get access to the white blood cells or antibiotics that kill bacteria, and you can develop chronic wounds and infections.
A common source of infection when patients are on chemotherapy is the catheters and medical hardware that we put in patients to help treat the cancer. For example, the skin overlying the portacath can become infected. Stents that we put into the bowel or the ureters can become infected from the bacteria in your bowel or ureters when the white count gets too low. That’s why your doctor will constantly ask you whether you have any indwelling catheters, stents, or any hardware when you have an infection.
Immunotherapy
One of the most exciting advances in cancer care is the development of immunotherapy, in which treatments use the body’s own immune system to help kill cancer cells. For decades, researchers studied cancer cells in isolation, wondering why they grow and mutate the way they do. Recently, researchers have focused on the fact that cancer cells don’t exist in isolation. They interact with the body’s other systems, including the immune system. New research focuses on the ways in which certain cancer cells can essentially fool the immune system into leaving them alone instead of killing them off as defective. This research has yielded some dramatic success stories in particular types of cancer.
One downside of immunotherapies is that they work in a minority of patients. The other downside is that newly empowered immune cells may attack healthy tissues as well, for example, in the tissues in the colon they can cause infections that mimic colitis. If you are undergoing immunotherapy, your doctor will talk to you about the risks of developing these secondary infections and how to manage them.
Infections after Bone Marrow Transplants
Some treatments alter the immune system in profound ways. The most extreme example of this is bone marrow transplantation, which replaces the damaged bone marrow stem cells with healthy cells either from a donor or from your own body. You might need a bone marrow transplant if the treatment requires high doses of chemotherapy that will destroy the bone marrow that creates all of your blood cells. In theory, these high doses of chemotherapy work more effectively against some cancers than do standard doses.
There are two methods for replacing bone marrow: autologous and allogeneic. An autologous transplant is one in which doctors collect your own stem cells circulating in your bloodstream and then replace them after the chemotherapy. Stem cells are the mother cells from which all components of the bone marrow come. So, an autologous procedure is not a transplant in the strict sense of the word, and there won’t be any need to search for a donor. Instead, doctors will set up an apheresis machine that looks like one used for a blood transfusion, but it will be collecting the stem cells circulating in your blood to be replaced after chemotherapy.
An allogeneic transplant starts with the high doses of chemotherapy, and then your stem cells are replaced by those of a donor who is genetically similar to you. Both procedures take about two weeks for your infused stem cells to repopulate your bone marrow, and during that time you will be at high risk of developing bacterial and sometimes fungal infections. After your bone marrow is fully functioning, your risk of infection will decline and eventually return to normal.
These new stem cells eventually become your new immune system. The hope is that these new white blood cells will recognize leukemia and lymphoma cells and attack them, while leaving the rest of the body relatively unharmed. We call these transplanted cells the graft cells, and we refer to the patient as the host of these new cells. If these grafted cells attack the normal cells of the host body, we call this graft versus host disease, and it is a possible outcome from transplantation.
If this happens, your oncologist will have to give you immunosuppressants to weaken your immune system and prevent it from attacking normal cells. But too much immunosuppression may make you prone to infections and also prone to the leukemia and lymphoma coming back. Too little immunosuppression, and you can suffer through terrible graft versus host disease. It really is a balancing act.
When we alter people’s immune system with an allogeneic bone marrow transplant, infection is one of the consequences. People can get infections from normal bacteria, atypical bacteria, fungi, and viruses. These infections can be quite severe and even lethal. The oncologists who perform bone marrow transplants are part of their own unique subspecialty. They are more like infectious disease doctors than oncologists in many respects. Ultimately, your graft will take hold, and your body will get used to your new bone marrow. More importantly, your new bone marrow will get used to you. At this point you will get fewer infections and eventually be able to resume a normal life.
Infections from Cancer
Growing tumors are notorious for creating infections. If a tumor grows in such a way that it reduces the blood flow to an organ, an infection will likely follow, and any injury caused by the tumor won’t be able to heal properly. Tumors can also block the ducts that drain secretions from organs such as the liver. That’s what happened to Amy, who was my patient several years ago. She was in her late fifties and under treatment for pancreatic cancer that was becoming resistant to treatment. She came to the clinic one day with slightly yellowed eyes. Blood tests showed that she had elevated bilirubin, a yellowish substance in the bile produced by the liver, and an ultrasound showed dilated biliary ducts, which help the liver drain waste. The biliary system is like a tree with one long trunk that divides off into two main trunks and then hundreds of small branches. In fact, doctors refer to it as the biliary tree. Unfortunately, the cancer was growing in several places and couldn’t be surgically removed. Amy soon developed shaking chills and came back to the clinic, where we found that the blockage had caused an infection. Surgeons were able to put a stent across the duct and open it up, and she felt much better afterward. Still, she continued to develop infections during the next year as the tumors grew, and this is one of the ways that you know the cancer is advancing. You continue to develop infections even though your immune system is working fine. When this happens, your medical team will try to find a way to drain the infection, but this may involve surgery.
Managing Infection as Cancer Progresses
Ron was a seventy-eight-year-old man with lung cancer when I met him as the attending physician on the cancer ward. He had been in treatment for a couple of years when scans revealed that his chemotherapy wasn’t holding his cancer steady any longer. Ron had decided to take a break from treatment for a while before deciding whether to enroll in a clinical trial, and, like many patients who take a break, he had immensely enjoyed time away from the infusion unit and the blood tests and the side effects of chemo. He was also looking forward to his youngest daughter’s wedding the following month, which is why he had avoided calling the clinic when he developed a persistent cough. The cough kept him up for two nights, but he told his oncologist that he didn’t feel short of breath, no more than normal, although he admitted that he wasn’t moving around all that much. He was reluctant to come into the clinic for tests because he was afraid that he would be hospitalized and miss the wedding.
His oncologist convinced him to come in for blood tests to rule out an infection, but they revealed an elevated white blood count, and a chest X-ray showed pneumonia. So Ron did have to be admitted for what he hoped would be a short stay. When I examined him a couple of days later, I couldn’t hear any sounds at all in that lower quadrant of his left lung, and I ordered a chest CT, which showed that the left lung had collapsed because a tumor had wrapped around the left lower airway. The tumor was preventing him from coughing up the bacteria that was feeding his pneumonia. When a tumor is the cause of this kind of infection, you can take antibiotics to kill some of the bacteria and contain the infection for a little while, but antibiotics alone will never cure it. The bacteria will soon become resistant to antibiotics, and then the infection will spread. Doctors call this a “closed space infection,” or abscess, and it’s a fairly common scenario as cancer progresses.
Ron and I had a conundrum. I knew that he wanted to attend a wedding in four weeks. The entire nursing staff of the cancer ward knew the date of the wedding, and so did every member of Ron’s medical team. We all wanted him to meet his goal of standing up with his daughter on her big day. Yet to give him the best chance of surviving the infection, we needed to figure out a way to open up his lung and drain out the bacteria. Ron wasn’t happy to hear any of this. He understood that at his age it was a risk to undergo a surgical procedure, but it was a bigger risk to hope the antibiotics would keep him alive.
Our interventional pulmonologists were able to get a stent into his bronchus to open it up, and then our radiation oncologists recommended radiation to the area to kill the cancer cells that were wrapping around the bronchus. Ron felt a little defeated at first from all of these interventions. He didn’t want to have to recover from anesthesia or endure weeks of radiation appointments. No one does. But he did all of it with his goals and values in mind. He knew his priorities and what he was willing to go through to be able to take part in this huge family celebration. When cancer progresses, it’s important for patients to be clear about what they want and what they value, because they can better choose the procedures that will be most effective for them.
Can I Die from Infection?
You can die from a runaway infection if it’s not treated, and that’s why doctors will urge you to be in contact with the clinic constantly about new symptoms and any fevers or shaking chills.
Some patients ask how people ultimately die from cancer, and infection is a common cause of death. Once cancer cells have stopped responding to treatment and are growing through various organs, they are even more likely to cause infections, and those infections become difficult to control without surgery and radiation. Early in your treatment, when the chemotherapy is controlling the cancer, you may be more willing to undergo these interventions, but at some point—months or years from now—you may not. The point is to stay in active discussions with your medical team and your family about your goals for treatment and how many hospitalizations you want to go through.