Immunizations and Prevention of Infection in Lupus

Infection is responsible for approximately 25% of all deaths in patients with SLE, up to 58% in developing countries, making it a leading cause of mortality among patients with SLE.¹^–³ Many infections in patients with SLE could be prevented with timely vaccinations, reducing exposure to contagious contacts, screening for latent infections, minimizing exposure to corticosteroids, targeted prophylaxis for high-risk patients, and, unless contraindicated, antimalarial therapy as standards of care.⁴ A checklist has been proposed for identifying high-risk patients and identifying prevention opportunities (Table 52-1).⁵ Vaccination status, particularly annual inactivated influenza and periodic pneumococcal vaccinations for patients taking immunosuppressants, has been included by expert consensus in the quality indicator set for SLE.⁶ Recommendations for specific vaccines in patients with SLE follow guidelines for the general local population, except when the patient is immunosuppressed, in which case the evidence-based guidelines from European League Against Rheumatism (EULAR) provide guidance on vaccines for adult and pediatric patients (Online Supplement 1).^7,⁸

TABLE 52-1 Checklist to Identify Patients with Systemic Lupus Erythematosus at Risk for Preventable Infections

HAS THE PATIENT HAD …	IF NOT …
Yearly influenza vaccination	Administer vaccine or recommend to primary care provider.
Pneumococcal vaccination	Administer vaccine or recommend to primary care provider (every 5 years).
Regular Papanicolaou (PAP) smears to screen for cervical dysplasia caused by human papillomavirus (HPV)	Recommend to primary care provider or gynecologist. Consider Gardasil vaccination.
Negative tuberculosis (TB) skin test before starting immunosuppressive agent	Treat with isoniazid for patients with evidence of latent TB infection.
Hepatitis B serologic testing	Obtain baseline serologic findings in all patients.
Hepatitis C serologic testing	Obtain baseline serologic findings in all patients with risk factors.
Human immunodeficiency virus (HIV) serologic testing	Obtain baseline serologic findings in all patients with risk factors.
Screening for Strongyloides in patients from endemic areas before starting immunosuppressive therapy	Obtain Strongyloides serologic finding, and treat with ivermectin if infected.

From Barber C, Gold WL, Fortin PR: Infections in the lupus patient: perspectives on prevention. Curr Opin Rheumatol 23:358–365, 2011.

A comparison of immunization rates among insured women with SLE, women in the general population, and women with nonrheumatic chronic conditions found similar rates of influenza (59%) and pneumococcal (60%) immunizations among those who were eligible in each group; however, overall rates were low and even lower in those of younger age and lower educational attainment.⁹ Not surprisingly, having seen a generalist during the preceding year increased the likelihood of receiving vaccinations, but the overall vaccination rate was still only 61%.

Ruiz-Irastorza and colleagues ¹⁰ reported the clinical predictors of major infections found in a prospective cohort of patients with SLE from Spain. The prevalence of life-threatening infections appears to be highest within the first 5 years of disease onset.^1,¹¹ Often, the infections that lead to hospitalization and/or death among patients with SLE are caused by common pathogens such as Streptococcus pneumoniae and Haemophilus influenzae, for which effective vaccinations exist.² Therapy for patients with SLE has shifted to include a greater use of biologics, which, as a class, tend to increase the risk for infection risk, but longer patient exposure is needed to determine whether this shift has altered infection outcomes in those with SLE.¹²

Are There Vaccinations That Should Be Avoided with Systemic Lupus Erythematosus?

More research is needed on the safety and efficacy of live attenuated vaccines (e.g., measles, mumps, rubella, herpes zoster, yellow fever, nasal-spray influenza vaccine) in patients with SLE and other autoimmune diseases who are taking immunosuppressive drugs. Household transmission from someone who has received a live attenuated virus living in close contact with a patient with SLE is rare, and contact precautions during viral shedding (typically 7 to 10 days) are recommended only for those who are severely immunosuppressed.¹³

Should Patients with Systemic Lupus Erythematosus Receive the Varicella Zoster Vaccine?

Reactivation of latent varicella zoster virus is one of the most commonly reported viral infections in SLE and may be complicated by disseminated disease, superinfection, and postherpetic neuralgia. A live attenuated herpes zoster vaccine came to market in 2006, and guidelines from the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices recommend vaccination in patients over 60 years of age, 2 to 4 weeks before any anticipated immunosuppression. The immunosuppression threshold, below which the administration of the herpes zoster vaccine is not contraindicated, includes prednisone less than 20 mg/day lasting less than 2 weeks, low doses of methotrexate (≤0.4 mg/kg/wk) or azathioprine (≤3.0 mg/kg/day).⁵

What Is the Risk of a Vaccination Triggering a Lupus Flare or Being Ineffective?

Apprehensions concerning vaccine safety and inefficacy, especially in an immunocompromised host, may be contributing to the low vaccination rates seen among patients with SLE. Despite anecdotal cases of disease exacerbations after vaccinations, multiple studies in different SLE populations have shown vaccinations against influenza, pneumococcal disease, and hepatitis B to be safe but efficacy to be potentially impaired.^14,¹⁵

Several studies have shown that influenza vaccination is safe and does not lead to SLE flares, with the majority of patients developing protective antibodies. In a prospective study of 72 patients with SLE, influenza-specific antibody responses were determined 2, 6, and 12 weeks after vaccination.¹⁶ Compared with high responders, low responders were more likely to have European-American backgrounds, be taking prednisone, have hematologic criteria for SLE, and have evidence of increased disease flares.

Similarly, several small studies have shown the vaccination against Pneumococcus to be safe in patients with SLE. The studies to date in SLE involve the 23-valent polysaccharide vaccine that shows good biologic tolerability of the vaccine with approximately 80% having an antibody response.¹⁷ In an efficacy study of 19 patients, titers of antibodies against the polysaccharides are significantly lower at 1, 2, and 3 years after vaccination in patients with SLE, compared with controls.¹⁸ Because reduced antipneumococcal antibody production has been reported in patients with SLE, consideration may be made for using the more strongly immunogenic vaccines, although they are not yet studied in SLE.

The hepatitis B vaccine has been shown in both a case-control study of 265 patients and a prospective cohort study of 28 patients not to be associated with the development of SLE or an exacerbation of existing disease.^19,²⁰ No loss of efficacy among patients with SLE is observed, with 93% having adequate anti–hepatitis B surface antigen antibodies after the series of three vaccinations and the remaining 7% having adequate antibody response after a fourth vaccination.²⁰

Vaccinations should not be withheld because of misguided fears of precipitating SLE flares. Although the immunologic response may be dampened by concomitant immunosuppressive medications, always addressing the immunization status in patients with SLE is best practice, regardless of their age or other risk factors. Immunogenicity is generally lower among vaccinated patients with SLE, compared with controls, especially for those patients receiving immunosuppressant agents; therefore a booster vaccination later in the influenza season or additional or more frequent vaccinations against other pathogens may be considered.¹⁵

Antibiotic Prophylaxis in Lupus

The ability of antimicrobial prophylaxis to prevent infection is important for patients with SLE but should be limited to specific, well-supported indications to reduce unnecessary toxicity, costs, and antimicrobial resistance. Indications for the use of antimicrobial prophylaxis and the recommended antibiotic regimens for patients with SLE are consistent with those of the general population,²¹ with a few exceptions in which patients with SLE are at a higher risk of opportunistic infections (see detailed text later in this chapter).

Approximately 30% to 38% of patients with SLE will have cardiac vegetations, most of which are asymptomatic but still put them at risk of endocarditis.^22,²³ This is especially true for patients with antiphospholipid antibodies, who are at an increased risk of cardiac vegetations.²⁴ However, the 2007 Antibiotic Prophylaxis Guidelines for preventing endocarditis published by the American Heart Association and the Infectious Diseases Society of America recommend antibiotic prophylaxis for a more limited number of conditions, compared with previous guidelines (Box 52-1). The presence of a murmur or aseptic vegetation alone no longer warrants antibiotic prophylaxis, based on subsequent studies that show a higher risk-to-benefit ratio than previously estimated.²⁵

Box 52-1

Cardiac Conditions Associated with the Highest Risk of Adverse Outcomes from Endocarditis for which Prophylaxis with Dental Procedures * Is Reasonable^†

Prosthetic cardiac valve or prosthetic material used for cardiac valve repair

Previous infectious endocarditis

Congenital heart disease (CHD), only if one of the following conditions is present:

• Unrepaired cyanotic CHD, including palliative shunts and conduits

• Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or catheter intervention, during the first 6 months after the procedure

• Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device, which inhibits endothelialization

Cardiac transplantation recipients who develop cardiac valvulopathy

^* Includes all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa.

^† Conditions, for which antibiotic prophylaxis is recommended, follow the 2007 Antibiotic Prophylaxis Guidelines for preventing endocarditis and is published by the American Heart Association and the Infectious Diseases Society of America.²⁵

Are There Specific Infections of Concern Requiring Prophylaxis in Patients with Systemic Lupus Erythematosus?

Additional infection risks may also warrant antibiotic prophylaxis in patients with SLE. Patients with latent Mycobacterium tuberculosis or with Strongyloides stercoralis should be given preventive therapy before starting immunosuppression therapy.⁵ Immunosuppressed patients with SLE are also at risk of developing Pneumocystis jiroveci pneumonia (PJP), and expert opinion suggests PJP prophylaxis be considered for patients with SLE taking 16 mg or more prednisone or equivalent for 8 weeks or longer with special consideration to those receiving cyclophosphamide.²⁶ A retrospective study of Pneumocystis carinii pneumonia (PCP), which included 119 patients with SLE, estimated the number needed to treat was 14 immunosuppressed patients with trimethoprim-sulfamethoxazole (TMP-SMX) to prevent one case of PJP.²⁷ They used once daily dosing of single-strength TMP-SMX and found a lower rate of allergic reactions, compared with previous reports, and no increase in SLE flares among those exposed to TMP-SMX. A metaanalysis of randomized controlled trials, including 1245 immunocompromised patients with non–human immunodeficiency virus (HIV), concluded that PJP prophylaxis with TMP-SMX is highly effective at preventing PJP infection, but it was only warranted when the PJP risk was over 3.5%. Based on an estimated PJP rate of 1.0% for the general population of patients with SLE, the number needed to treat (n = 110) would be greater than the number needed to harm (n = 32) because of adverse reactions and intolerance to TMP-SMX.²⁸ Similar conclusions came from a review of the literature on PJP in SLE and a survey of U.S. rheumatologists in which investigators found a low incidence of PJP in patients with SLE, yet a high prevalence of rheumatologists routinely prescribing TMP-SMX for patients receiving cyclophosphamide.²⁹ Until consensus guidelines are in place, the decision to use PJP prophylaxis with TMP-SMX in patients with SLE will depend on the individual assessment of known risk factors for PJP weighed against the potential risks of TMP-SMX. (See detailed discussion later in this chapter.)

Are There Antibiotics That Patients with Systemic Lupus Erythematosus Should Avoid?

Exposure to antibiotics is unavoidable for a majority of patients with SLE, who are more prone to develop infections as a result of disease-related altered immune responses and immunosuppressive medications. However, certain antibiotics carry a higher likelihood for being problematic for patients because of their sun-sensitizing properties, their ability to provoke drug allergies, or their potential to trigger disease flares. Sun-sensitizing antibiotics that can flare cutaneous and occasionally systemic disease include tetracyclines, sulfonamides, and fluoroquinolones. This property alone would not be an absolute contraindication for patients with SLE but would make sun-protective measures (e.g., sun avoidance, sun-protective clothing, broad-spectrum sunscreen) even more of a priority. Minocycline is also associated with causing drug-induced lupus; however, no evidence suggests that these drugs are implicated in drug-induced lupus or precipitate flares in patients with established SLE.³⁰

A case-control study of antibiotic allergy in 221 patients with SLE found that patients exposed to antibiotics reported significantly more penicillin and cephalosporin (27% versus 10% and 15%), sulfonamide (32% versus 14% and 12%), and erythromycin (13% versus 3% and 3%) antibiotic allergy, compared with either exposed related or unrelated controls.³¹ The increased frequency of tetracycline allergies reported by exposed patients with SLE, compared with either control group (7% versus 4% and 3%), was not statistically significant. Consistent with several previous and subsequent reports, sulfonamide antibiotics were the most likely class of antibiotics to trigger an allergic reaction among patients with SLE^19,^32,³³ and the most likely to exacerbate SLE with photosensitive rashes and cytopenias being the most common confirmed exacerbations associated with antibiotic exposure.^31,³⁴ Although completely avoiding their use would be unrealistic, they should be used sparingly and with caution, because sulfonamide antibiotics are known to sun-sensitize, provoke allergic reactions, and cause disease flares among patients with SLE.

Only gold members can continue reading. Log In or Register to continue