During this session, Barry Brause, MD, Director of Infectious Diseases at Hospital for Special Surgery, presented a comprehensive overview and update on infectious disease prevention, especially with regard to people with systemic lupus erythematosus (SLE, or more commonly called lupus). He reviewed various infectious diseases, covering the ways that these diseases spread, the different types of vaccinations available, and recommendations for protecting yourself from infectious diseases – with a special emphasis on people with lupus.
Sections of this article:
- Higher risk of infection in patients with rheumatic disease
- Vaccinations in people with rheumatic diseases
- Do vaccines cause lupus flares?
- Types of infectious diseases and available vaccines
- Prosthetic joint infection prevention
Higher risk of infection in patients with rheumatic disease
Dr. Brause began his presentation by describing how patients with rheumatic diseases, such as lupus, have a higher risk of infection. The increased risk is related to the suppression of the immune system (also called immunosuppression), due to the underlying disease and the associated treatment. Treatments that suppress the immune system may include the following:
- disease-modifying antirheumatic drugs (DMARDs), for example, methotrexate, leflunomide (Arava), azathioprine (Imuran), cyclosporine
- biologic agents (also called biologic drugs or "biologics") – for example, anti-TNF agents such as etanercept (Enbrel) or adalimumab (Humira)
Immunosuppressive drugs (also called immunosuppressants or antirejection medications) for lupus specifically include the following:
- azathioprine (Imuran, Azasan)
- belimumab (Benlysta) – biologic agent
- corticosteroids (prednisone)
- cyclophosphamide (Cytoxan)
- methotrexate (Trexall, Rheumatrex)
- mycophenolate (CellCept, Myfortic)
- rituximab (Rituxan) – biologic agent
Biologics are distinguished from other immunosuppressants in that they are produced by living systems, such as bacteria or plant or animal cells. As soon as a patient starts to modify their immune system through the use of these drugs, they also modify their immune system’s ability to fight off and prevent infection.
Immunosuppressive drug therapy can increase the risk of infection, including:
- bacterial sepsis
- mycobacterial tuberculosis (TB) infection recrudescence
- fungal infection/reactivation (histoplasmosis, coccidioidomycosis, blastomycosis, aspergillus, Candida)
- viral reactivation, for example, varicella-zoster virus (shingles) or worsening of a chronic viral infection (for example, hepatitis B infection)
If a patient acquires a serious infection while taking a biologic agent, that therapy will be suspended. If the prescribing physician feels it is appropriate, the patient may return to using the biologic drug once the infection is under control.
Similarly, whenever there is a risk of surgical-site infection, certain immunosuppressive agents, such as biological drugs, may be suspended before or after surgical procedures in order to reducethe risk of infection. The patient will resume using the drug therapy after the surgical site has healed.
Vaccinations in people with rheumatic diseases
There is no evidence that vaccinations commonly cause a flare of autoimmune disease, and specifically in rheumatic conditions like rheumatoid arthritis and lupus. This is true of:
- pneumococcal vaccine (killed), commonly called the “pneumonia vaccine”
- influenza vaccine (killed), commonly called the “flu shot” or “flu vaccine”
Both of these vaccines are strongly recommended for people with inflammatory rheumatic diseases like lupus. This is because these patients have disease-related increased morbidity and mortality from respiratory infection. That is, they have a heightened risk of respiratory infection, including severe illness and, rarely, death. The Tdap vaccine for tetanus, diphtheria and pertussis (whooping cough) is routinely given once in adulthood, and is helpful for patients taking immunosuppressive agents.
Do vaccines cause lupus flares?
For those with lupus, vaccinations do not commonly make lupus more active. Dr. Brause recommended that patients get vaccinated when they are not experiencing an active lupus flare. He strongly advised against getting vaccinated when there is active lupus nephritis (kidney inflammation). Although uncommon, HBV, HPV and Norwalk agent vaccines have been known to induce disease flares.
According to Dr. Brause, killed vaccines (also called inactivated vaccines), which are vaccines that do not have any live components in them at all – are safe and effective for people with lupus. Specifically, pneumococcal, influenza (“flu”) and hepatitis B vaccines are recommended by the American College of Rheumatology.
Live vaccines, however, are not recommended for lupus patients, due to the increased risk of infection from the vaccine. They should generally be avoided. In most cases, there are suitable killed vaccines that may take the place of live vaccines.
Live vaccines to avoid
Live vaccines to be generally avoided are listed below. Patients should talk with the physician caring for their lupus before considering any of the following:
- measles, mumps, rubella
- yellow fever
- varicella, herpes zoster (Zostavax)
- live attenuated influenza vaccine (LAIV) – however, a killed vaccine is available
- typhoid (oral, Ty21a) – however, a killed vaccine version is available
- polio (oral, Sabin) – however, a killed vaccine version is available
Types of infectious diseases and available vaccines
- Pneumococcal infections
- Hepatitis B virus
- Herpes zoster (shingles)
- Tetanus, diphtheria and acellular pertussis
Streptococcus pneumonia (pneumococcus) is the leading cause of vaccine-preventable illness and death in the United States. Pneumococcal infections can cause pneumonia and other respiratory conditions, blood infections and meningitis. Pneumococcal infections are transmitted from person to person by respiratory droplets, as can be spread by a cough. Those who are at greater risk include people who:
- are aged 65 years and older
- consume large quantities of alcohol
- smoke tobacco
as well as people who have any of the following conditions:
- heart or lung disease
- sickle cell disease
- alcoholism, cirrhosis
- cerebrospinal fluid (CSF) leaks
- cochlear implants
- lymphoma or leukemia
- kidney failure
- HIV infection
- damaged or no spleen
- immunosuppressive diseases or treatments
Types of pneumococcal vaccines
Pneumococcal polysaccharide vaccine (PPSV23) is the older of the two vaccines currently available.
- Dosage information: The use and timing of this vaccine should be discussed with your doctor.
- Side effects:
- About 50% of patients experience redness or pain at injection site.
- Muscle aches can occur.
- Less than 1% have more serious local reactions or allergic reactions.
Pneumococcal conjugate vaccine (PCV13 or Prevnar 13®) is a recently released vaccine designed to give more immunity and a stronger antibody response than the PPSV23 vaccine, but it has a narrower range of strains.
- Dosage information: The use and timing of the dose should be discussed with your doctor.
- Side effects:
- redness, pain and/or swelling at the injection site
- muscle aches
Influenza (“flu”) has the capacity to cause a large amount of inflammation of the:
- bronchial passageways of the lungs, with mucosal edema (swelling of the mucus membranes)
This disease can damage and weaken the cells lining the respiratory tract, so that they will not protect people as well as healthy cells. This creates greater risk that a person will develop influenza pneumonia or bacterial pneumonia.
Complications of flu
Influenza can lead to further complications, including:
- primary influenza viral pneumonia
- bacterial superinfection pneumonia
- exacerbation of chronic pulmonary disease
Additional, uncommon complications include:
- Guillain-Barré syndrome
- Reye’s syndrome
- transverse myelitis
People who have a higher priority to receive influenza vaccine include:
- pregnant women
- persons providing care for infants less than six months of age
- healthcare emergency medical services personnel who have direct contact with patients or infectious material
- children aged 6 months to 4 years
- adults over 65 years old
Medical conditions that put people at higher risk for influenza-related complications include:
- neurologic disorders
- chronic lung disease
- heart disease
- blood disorders
- kidney or liver disease
- metabolic disorders or obesity
- weakened immune systems or are on chronic steroid or other immunosuppressive therapy
Influenza may be transmitted through saliva, nasal secretions and feces. Sneeze and cough particles can travel up to three feet. An infected person is contagious 24 hours prior to and up to seven days after symptoms of disease onset. Viruses can also continue to live days or even weeks on dry surfaces. A person is most likely to be exposed by touching a contaminated surface and then touching one’s nose, eyes or mouth.
Transmission of influenza can be prevented by thorough and frequent hand washing and by coughing into a barrier such as a tissue or elbow. One should stay informed about flu season, avoid touching eyes, nose and mouth, and avoid close contact with those who are infected – even if that person is on antiviral therapy. One should stay home if ill. Lastly, one can get vaccinated!
Side effects of influenza vaccines
- Some people experience pain and inflammation at the injection site.
- 5% experience fever.
- 3% to 12% experience malaise.
- 2% to 9% experience myalgias (muscle pain).
- 5% to 6% experience arthralgias (joint pain).
- The above side effects can begin six hours after vaccination and can persist for two days. Resolve with aspirin, acetaminophen (Tylenol) or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil).
- Allergies such as hives may occur, but these reactions are rare unless you are allergic to eggs.
- Guillain-Barré syndrome may occur, but the incidence is very low.
Live influenza vaccinesare not recommended
Dr. Brause strongly advised against the use of live influenza vaccines in people who are immune suppressed. This is because live, attenuated vaccines can be a danger to such patients. He also shared that the influenza vaccination in the form of the quadrivalent nasal spray (usually recommended for those aged 2 to 49 years old), can be less effective than the others. Lastly, he said there are no available vaccines that cover H3N2v influenza (a swine flu variantassociated with people who have hadcontact with pigs) or H7N9 (also called avian influenza or bird flu, active inChina only).
Current flu season – Vaccine updates
For updates on vaccines for the current flu season, visit the Flu Season webpage of the Centers for Disease Control and Prevention (CDC).
Hepatitis B virus (HBV) infection risks with biologic agents
Patients should be screened for viral hepatitis before biologic agents are started. This is a routine practice. In patients with hepatitis B, treatment with biologic agents may increase viral growth, worsening the disease. Therefore, biologic drugs should be avoided until the hepatitis B is being managed, and only with approval by a specialist in hepatitis. If there is a possibility that a patient might contract hepatitis B, the patient should be vaccinated. There is an effective killed vaccine available.
Herpes zoster (shingles)
Shingles is the reactivation of the chicken pox (varicella) virus. Once a person gets chicken pox and recovers from it, the virus continues to stay in the body forever, remaining inactive in nerve cells. At some point in life, it might start to multiply in the nerve and appear as a band-like skin eruption on the body surface. Shingles is associated with aging, since the immune system loses some strength with age. In addition, taking immunosuppressive agents increases the risk for shingles.
After a shingles infection, some patients develop a severe pain syndrome in the area where they had the rash. This is called postherpetic neuralgia. Any person diagnosed with shingles should receive immediate antiviral treatment. This canreduce the risk of postherpetic neuralgia.
A shingles vaccine can help prevent shingles from occurring and, when shingles does occur, it can make it less likely for a patient to experience the pain of postherpetic neuralgia.
Until recently, it was not so easy for a person with rheumatic disease to protect themselves from shingles because only live vaccines were available. With the introduction of Shingrix (a killed vaccine for shingles), this may change. Unfortunately, however, no shingles vaccine has yet been approved by the CDC for use in immunosuppressed people.
Screening for herpes zoster vaccine eligibility
Screening for a history of chickenpox is not necessary in order to administerthe vaccine to a person 50 years of age or older. Those who were born in the United States before 1980 are assumed to have been exposed to chickenpox regardless of whether they recall having the chickenpox.
Complications of herpes zoster (shingles) infection
Complications of shingles include:
- postherpetic neuralgia, which can persist for weeks or months after rash resolves
- ophthalmic zoster, which is the involvement of the ophthalmic division of the trigeminal nerve and the eye
- dissemination with generalized skin eruptions and involvement of the central nervous system, lung, liver and pancreas
Herpes zoster (shingles) vaccines
- contains live attenuated varicella virus in an amount that is approximately 14 times greater than that in regular varicella (chickenpox) vaccine
- approved for persons 50 years and older
- administered by an injection under the skin (subcutaneous).
- effectiveness decreases with age
- cannot be used in immunosuppressed persons
- a newer vaccine (licensed in 2017)
- considered safer than Zostavax, as it is not a live vaccine, and effectiveness not decreased with age
- given as a two-dose regimen, with the second dose given 2 to 6 months after the first dose
- indicated for immunocompetent patients greater than 50 years old
- not yet approved for use in immunocompromised patients (being studied)
Shingrix vaccine: effectiveness
Successful pevention of herpes zoster (shingles) inindividuals by age:
- 50 to 59 years old: 96.6%
- 60 to 69 years old: 97.4%
- 70 years old: 97.6% in the first year, 84.7% (after 1 to 3 years)
Successful prevention of postherpetic neuralgia in individuals by age:
- over 50 years old: 91.2%
- over 70 years old: 88.8%
Adverse events/reactions (grade 3):
- injection site reactions: 9.4% (placebo 0.3%)
- systemic reactions (such as myalgia, fatigue, fever, headache and gastrointestinal): 10.8% (placebo 2.4%)
- Overall: grade 3: prevented normal activities 16.5% (placebo 3.1%)
For those anticipating immunosuppression, Dr. Brause shared that, according to the US Centers for Disease Control’s Advisory Committee on Immunization, “zoster vaccine should be administered at least 14 days before initiation of immunosuppressive therapy, although some experts advise waiting a full month after zoster vaccination to begin immunosuppressive therapy.” (US Dept. of Health and Human Services, Public Health Service, Centers for Disease Control. Morbidity and mortality weekly report: MMWR, June 6, 2008.)
Patients need to consult with their doctors about the use of Shingrix in their particular situation.
Tetanus, diphtheria and acellular pertussis
Tetanus is a disease caused by bacteria that enters the body through breaks in the skin, and the symptoms are characterized by painful muscle spasms, breathing problems and paralysis and potentially death.
Diphtheria is a disease that causes a thick coating in the back of the nose or throat, making it difficult to breathe and swallow. It may also attack the heart and nerves.
Pertussis, also called “whooping cough,” is highly contagious. It causes prolonged, distinct coughing and remains incompletely controlled in the US. However, there are currently epidemics of pertussis across the world.
Tetanus, diphtheria and acellular pertussis (Tdap) vaccine
The Tdap vaccine acts as a defense against whooping cough, tetanus and diphtheria. It is recommended that this vaccine be given once in adulthood. It is not a live virus vaccine.
Side effects of Tdap vaccine
- pain (67%), redness, swelling at the injection site (20%)
- fever (1%)
- headache (40%)
- fatigue/tiredness (33%)
- nausea, vomiting, diarrhea (1% to 3%)
- body/joint aches
- swollen glands
Patients are advised not to take this vaccine if they have had a life-threatening allergic reaction after a dose of any tetanus, diphtheria or pertussis-containing vaccines or if they have had a severe allergy to any part of this vaccine.
Patients should not take this vaccine if they have had a coma or multiple seizures within seven days after a childhood dose of either the DTP or DTaP vaccines. (These are the tetanus, diphtheria and pertussis vaccines given to children under age seven. The, related, Tdap vaccine is a booster shot given years later to provide continued immunization from these diseases into adulthood.)
Dr. Brause advises those who have epilepsy, other nervous system problems, or if they have ever had Guillain-Barre Syndrome to check with their doctors before taking this vaccine. However, these problems are very uncommon.
Mycobacterium tuberculosis (TB) can present as active tuberculosis or it can be discovered by skin or blood testing to be a latent (inactive) infection. TB is usually a respiratory infection that starts in the lungs and slowly travels into the bloodstream and throughout the whole body. Latent tuberculosis means that a person has the infection, but it is not active – the infection is not visible and the infection is not felt by the infected person. The latent infection is particularly concerning to physicians because the patient is often unaware that they are infected.
Those with rheumatic diseases are more susceptible to TB or latent TB reactivations due to biologic agents, DMARDs and steroids they may take, whichcan diminish their immune system’s potency. Screening evaluations for latent or active TB infections should be conducted prior to starting immunosuppressive therapies in order to reduce the risk of reactivating latent TB. Other risks include:
- history of prior exposure to TB
- drug addiction
- HIV infection
- birth or extended living in a region of high TB prevalence
- working or living in high-risk settings for TB such as jails, homeless shelters and drug rehabilitation centers
Patients can be tested for latent TB, through a tuberculin skin test or blood test (interferon release blood assays such as QuantiFERON-TB Gold). If positive, treatment should be administered prior to any rheumatic disease-related immunosuppressive therapy that can interfere with immune function. Initiating anti-TB therapy one month prior to starting immunosuppressive therapy can substantially decrease the risk of latent TB reactivation.
Prosthetic joint infection prevention
Before a hip, knee or other prosthetic joint replacement surgery, Dr. Brause emphasized that a patient with a chronic dermatitis condition should see a dermatologist to make sure any skin conditions (such as psoriasis or eczema) are under optimal control. Any visible lesions or breaks in the skin can predispose a patient to infection. All dental needs, such as cleanings or dental procedures, should be addressed prior to the operation as well.
The most common types of infections which can be spread to the prosthetic joint through the bloodstream include:
- Skin problems.
- Teeth/gum problems.
- Urinary tract infections (UTIs). Any bladder procedures also need to be completed before surgery. If these procedures are not taken care of prior to surgery, an infection could travel through the bloodstream and infect the prosthesis.
During surgery, the care team will work to reduce the infection rate as best they can through the use of prophylactic antibiotics and laminar air flow. Prophylactic administration refers to the act of administering antibiotics prior to surgery in order to prevent infection. Laminar air flow is a system that filters and cleans the air in the operating room. (Learnmore about infection control andlowinfection rates at HSS.)
After joint replacement surgery, it is essential to visit the dermatologist if you have any chronic dermatitis condition. Thisis tomaintain intact skin and keep chronic dermatitis under control to prevent infection. It is also essential to keep teeth/gums healthy and take care of anyurinary tract infectionspromptly.
It is recommended that prophylactic antibiotic therapy be taken prior to certain dental and urological procedures for two years postimplantation. It is also recommended that prophylactic antibiotic therapy should be given prior to certain dental and urological procedures for the life of the prosthesis in all patients who are receiving immunosuppression treatment or who have:
- inflammatory arthritis
- insulin-dependent diabetes
- a history of prior prosthetic joint infection, hemophilia or malnutrition
If any of the above conditions apply to you, you should discuss this with your dentist or your urologist.
Dr. Brause concluded his talk by emphasizing the importance of protecting yourself from infectious diseases through vaccinations. Several vaccines can be beneficial and effective for people with rheumatic diseases such as lupus. Before making any decisions, however, it is essential to talk to your rheumatologist to ensure that you receive your vaccinations safely and appropriately.
About the HSS SLE Workshop
Originally presented January 24, 2019, at the HSS SLE Workshop, a free support and education group held monthly for people with lupus and their families and friends.
Summary by Asia Taylor
Masters of Social Work intern and SLE Workshop Coordinator
Department of Social Work Programs
Barry D. Brause, MD
Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College
- Reducing Risk of Infection in People With Rheumatoid Arthritis