Dr. Barry Waters*: I have a 21 yr. old lupus nephritis patient on mycophenolate, hydroxychloroquine and prednisone 40 mg per day. She says both her current nephrologist and her prior pediatric rheumatologist told her NOT to get pneumococcal and flu vaccines. I thought she is supposed to get them - any comment?
Dr. Kathryn Dao: The question regarding vaccinating patients with systemic lupus erythematosus (SLE) against influenza and pneumococcal infection is actually a common one. The concerns are whether vaccinations would flare the disease by stimulating an already dysregulated immune system and whether vaccinations are even effective particularly in the setting of aggressive immunosuppressive therapies.
We know that: 1) infection is one of the primary causes of death in patients with SLE; 2) patients with high disease activity or who are on corticosteroids, DMARDS, biologics are at greatest risks for infection; and 3) vaccinations are our greatest tools to prevent infection.
So what is the evidence for or against vaccinating SLE patients?
Influenza vaccination: Currently available influenza vaccines include: the trivalent, quadrivalent, high dose flu, and live-attenuated vaccines. The majority of these vaccines do not contain adjuvants designed to make vaccines more effective (note that only 1 flu vaccine has an adjuvant (Fluad), which recently got a nod from the FDA in September 2015 but currently is not available to the general public as of this publication). Adjuvants, by activating toll-like receptors and the NALP3 inflammasome, have been linked to Autoimmune (or Autoinflammatory) Syndrome Induced by Adjuvants (ASIA) characterized by fever, arthritis, myositis, rash, and in some cases, pericarditis and sclerodactyly in the presence of abnormal autoimmune serologies.
Hence, most studies looked at nonadjuvant vaccines in SLE patients. Many studies were conducted in patients with low disease activity and found that these vaccines are safe and effective in patients with SLE.
The question would be, what happens if you use a nonadjuvant vaccine in a patient with high disease activity? A few published case reports noted precipitation of SLE disease after vaccination; in addition, other studies found an increase in autoantibody levels after vaccination without clinical disease flares. However, these reports included only small numbers of patients (20-50 patients).
In a 2013 study by Campos et al., 118 juvenile SLE patients and 102 matched controls were vaccinated with nonadjuvant influenza A H1N1 vaccine; patients with higher SLEDAI-2K score >8, had higher rates of non-serocoversion (48.8% vs. 24%, p=0.008) compared to controls, but there were no worsening of SLE disease activity (1). Overall, patients with SLE had rate of seroconversion 63.6% compared to controls 91.2%; P < 0.001, comparable to other studies.
- Bottom line is, while the rates of seroconversion and seroprotection are lower than healthy controls, vaccinating with nonadjuvant flu vaccines is safe in patients with SLE and should be undertaken regardless of disease activity and degree of immunosuppression
- (avoid live vaccines in those who have contraindications, e.g. : patients with prednisone > 20 mg/day, on biologics).
Pneumococcal vaccination: The most common pneumococcal vaccines our patients need are the pneumococcal conjugate vaccine (PCV13 or Prevnar 13) and the pneumococcal polysaccharide vaccine (PPSV23 or Pneumovax). There are very few studies looking at pneumococcal vaccination in patients with SLE (2-4). These studies, again, included small numbers of patients. Overall, there were no disease flares in patients who were vaccinated. Side effects were mild. One study noted that antibody responses to pneumococcal vaccines were unaffected by prednisone, cyclophosphamide, and azathioprine. During the BLISS-76 trial, the response to pneumoccocal vaccination was evaluated. Patients receiving belimumab did not have a reduced antibody response, consistent with preservation of the memory B cell compartment with this drug.
- Bottom line: Patients with SLE should be vaccinated with the pneumococcal vaccine.
* Case submitted by Barry Waters, MD, from American Arthritis and Rheumatology Associates; He is also the Rheumatology Program Director at Larkin Community Hospital in Coral Springs, FL
1. Campos LM1 et. al. Arthritis Care Res (Hoboken). 2013 Jul;65(7):1121-7. doi: 10.1002/acr.21948.
2. Tarján P et al. Scand J Rheumatol. 2002;31(4):211-5.
3. Lipnick RN et al. J Rheumatol. 1985 Dec;12(6):1118-21.
4. BLISS-76 Study Group. J Rheumatol. 2012 Aug;39(8):1632-40. Epub 2012 Jun 15.