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Rita Baron-Faust, MPH, CHES

Advancing Wellness on Many Fronts

THE AUTOIMMUNE CONNECTION BLOG

Zika and Autoimmunity -- A New Viral Threat?

August 27, 2016
Tags: Zika virus, Zika risk in autoimmunity, Guillain-Barre' syndrome, GBS, immune thrombocytopenia purpura, ITP, acute disseminated encephalomyelitis (ADEM), Zika sexual transmission, Chikungunya-linked rheumatoid arthritis, Zika vaccine
As mosquito-borne Zika virus continues to spread in southern Florida and threaten other Gulf Coast states, its connections with autoimmunity are cause for concern.

In addition to causing birth defects and severe brain damage (microcephaly) in hundreds of babies born to Zika-infected women,1 the virus is also being blamed for an increase in cases of a rare autoimmune neurological disorder called Guillain-Barré syndrome (GBS).2

Viral infections have long been suspected as a potential cause of autoimmune diseases, notably Epstein Barr virus (EBV). Infections are also a frequent trigger for Guillain-Barré, which affects peripheral and sensory nerves, causing difficulty walking and temporary paralysis. The mechanism is thought to be “molecular mimicry,” in which the structure or proteins of a virus are similar to normal cells in the body, so the immune system not only attacks the virus, but also the healthy tissue.3

So far, 18 countries report an increased incidence of GBS associated with Zika, according to the World Health Organization.4 At least seven cases of Zika-associated GBS have been reported in the U.S.5 and 30 in Puerto Rico, one of them fatal. A public health emergency has been declared in Puerto Rico, with almost 11,000 cases of locally-acquired Zika, including more than 1,000 pregnant women.6

Researchers say a second rare, autoimmune neurological disorder -- acute disseminated encephalomyelitis (ADEM) -- may also be linked to Zika. ADEM, like multiple sclerosis, results from an autoimmune attack on the protective myelin coating on nerve cells in the brain and spinal cord.7

Zika has also been associated with cases of immune thrombocytopenia purpura (ITP), an autoimmune disease which causes destruction of platelets.8 Platelets help blood to clot and if too many are destroyed there’s a risk of serious hemorrhage. One death was reported in Puerto Rico from severe thrombocytopenia in an elderly man with a confirmed Zika infection.8

Systemic treatments for chronic autoimmune disease, especially biologic drugs, suppress an over-active immune system and carry a potential risk of serious infections, including tuberculosis. Just having an autoimmune disease puts you at risk of developing another.

So far, however, autoimmune patients don’t appear to be at particular risk from Zika, stresses Tyler M. Sharp, PhD, an epidemiologist with the Centers for Disease Control and Prevention (CDC) and co-author of a recent report on ITP and Zika.

“To date, there has not been a link established between having a history of autoimmune disease and developing either Guillain-Barré syndrome or immune thrombocytopenia purpura following Zika virus infection,” emphasizes Dr. Sharp. Still, he adds, “patients with pre-existing autoimmune disease should consult their physician before traveling to an area with ongoing Zika virus transmission.”

People Can Spread Zika, Too

Zika is an arbovirus similar to Dengue and yellow fever, carried by two types of mosquitoes -- Aedes aegypti found in southern and tropical climates and the more common Aedes albopictus mosquito, found in much of the U.S. But in the current Zika outbreak, human beings become unwitting disease carriers.

It's a dangerous cycle: A Zika-carrying mosquito bites and infects a human -- another mosquito bites that person and acquires Zika virus through a blood meal -- then that mosquito buzzes off to infect someone else.9 Since the virus doesn’t always cause symptoms, people may not even know they’ve been infected and the A. aegypti mosquito often bites multiple people in a single blood meal. That’s one reason Zika can spread quickly.9

Zika can also be transmitted sexually through semen and other body fluids, even before someone has symptoms of an infection -- and long after symptoms end.10 According to the CDC, Zika can remain in semen longer than in other body fluids (including vaginal fluids, urine, and blood). So safe sex, the use of condoms and other barrier methods, is highly advised in Zika-affected areas.11

Given the risks of sexual transmission, the Food and Drug Administration (FDA) is now calling for all donated blood in the U.S. to be tested for Zika.12

The Virus-Autoimmunity Connection

Zika isn’t the first mosquito-borne virus with an autoimmune connection.

Chikungunya virus and Dengue fever, arboviruses spread by the same mosquitoes as Zika, can cause joint pain and mimic other symptoms of rheumatoid arthritis (RA). Some people infected with Chikungunya have developed an inflammatory arthritis that can persist for months to years.13 A recent epidemic of Chikungunya in the Caribbean was associated with post-infection rheumatic and musculoskeletal disorders, including RA.14

While it’s possible that people with autoimmune diseases who become infected with Zika could develop GBS, the actual risks are unknown.

Also unknown: if Zika could pose a risk in people with suspected autoimmunity who haven’t been formally diagnosed. One recent study suggests that people with primary chronic ITP may be at an increased risk for infections up to 5 years before they are actually diagnosed.15

If people with an autoimmune condition -- or otherwise healthy individuals, for that matter -- have been in an area with ongoing Zika transmission and are pregnant or develop an illness consistent with Zika virus (fever, rash, joint pain, or conjunctivitis/red eyes) within a couple weeks after traveling, they should be evaluated by a clinician to determine if they should be tested for Zika, advises the CDC’s Dr. Sharp.

If you have an autoimmune disease and live in a Zika-zone (such as Miami-Dade County in Florida) or plan travel to such areas, “employ approaches to avoid mosquito bites, such as regular use of mosquito repellent, staying in areas that are air conditioned and/or have intact window screens, and wearing long sleeves and pants,” Dr. Sharp recommended in an email.

Right now, aerial spraying, removal of standing water and use of larvicides in affected areas are the best public health defense against mosquitos. While preliminary results from an early-phase clinical trial of a potential Zika vaccine are expected by the end of 2016, it could take several years for a vaccine to be approved by the FDA and enter the marketplace.16

Note: Read more about molecular mimicry and other suspected viral triggers of autoimmunity in "The Autoimmune Connection."

References

1 Centers for Disease Control and Prevention (CDC), Outcomes of Pregnancies with Laboratory Evidence of Possible Zika Virus Infection in the United States, 2016. http://www.cdc.gov/zika/geo/pregnancy-outcomes.html. Retrieved August 24, 2016.

2 Cao-Lormeau VM, Blake A, Mons S, et al., Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016;387:1531–39. http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00562-6.pdf. Retrieved August 24, 2016.

3 Anaya JM, Ramirez-Santana C, Salgado-Castaneda I, et al., Zika virus and neurologic autoimmunity: the putative role of gangliosides, BMC Medicine2016;14:49. DOI: 10.1186/s12916-016-0601-y. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0601-y. Accessed August 25, 2016.

4 WHO Situation Report, Zika Virus Microcephaly and Guillain-Barré Syndrome, August 25, 2016. http://www.who.int/emergencies/zika-virus/situation-report/25-august-2016/en/ Retrieved August 24, 2016.

5 CDC, Zika Virus Case Counts in the US. http://www.cdc.gov/zika/geo/united-states.html . Zika Virus and Guillain-Barré Syndrome. http://www.cdc.gov/zika/healtheffects/gbs-qa.html. Retrieved August 24, 2016.

6 HHS declares a public health emergency in Puerto Rico in response to Zika outbreak. Health & Human Services (HHS) Press release, August 12, 2016. https://www.hhs.gov/about/news/2016/08/12/hhs-declares-public-health-emergency-in-puerto-rico-in-response-to-zika-outbreak.html. Retrieved August 24, 2016.

7 Zika Virus May Now Be Tied to Another Brain Disease, American Academy of Neurology Press Release, April 10, 2016. Abstract Title: Neurologic Manifestations of Arboviruses in the Epidemic in Pernambuco, Brazil. Author: Brito Ferreira ML. https://www.aan.com/PressRoom/home/GetDigitalAsset/12051. Accessed August 27, 2016.

8 Sharp TM, Muñoz-Jordán J, Perez-Padilla J, et al., Zika Virus Infection Associated with Severe Thrombocytopenia. Clin Infect Dis. (2016) doi: 10.1093/cid/ciw476. First published online: July 14, 2016.

9 Peterson LR, Jamieson DJ, Powers AM, Honein MA. Review Article: Zika Virus. N Engl J Med 2016;374:1552-63. DOI: 10.1056/NEJMra1602113.

10 CDC. Zika and Sexual Transmission. http://www.cdc.gov/zika/transmission/sexual-transmission.html. Retrieved August 25, 2016.

11 Brooks JT, MD1; Friedman A, Kachur RE, et al., Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus — United States, July 2016. MMWR, July 29, 2016;65(29):745-747.

12 FDA advises testing for Zika virus in all donated blood and blood components in the US. FDA News Release, August 26, 2016. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm518218.htm Retrieved August 26, 2016.

13 Miner JJ, Aw-Yeang HX, Fox JM et al., Brief Report: Chikungunya viral arthritis in the United States: A mimic of seronegative rheumatoid arthritis. Arthritis Rheumatol. 2015; 67(5): 1214–1220. doi:10.1002/art.39027.

14 Foissac M, Javelle E, Ray S, Guérin B, Simon F. Post-chikungunya rheumatoid arthritis, Saint Martin [letter]. Emerg Infect Dis. 2015 Mar. http://dx.doi.org/10.3201/eid2103.141397.

15 Ekstrand C, Linder M, Cherif H, et al. Patients with chronic ITP may have increased infection risk before diagnosis. J Thromb Haemost. 2016;14(4):807-814. doi:10.1111/jth.13267.

16 Safety and Immunogenicity of a Zika Virus DNA Vaccine, VRC-ZKADNA085-00-VP, in Healthy Adults. https://clinicaltrials.gov/ct2/show/NCT02840487 Retrieved August 24, 2016.
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Alopecia Areata – Losing Hair, Not Hope

August 19, 2016
Tags: Alopecia areata, baldness, hair loss, hair loss treatments, hair loss drug clinical trials, reversing hair loss, FDA-approved drugs may reverse hair loss
Going bald can be emotionally upsetting for anyone. But imagine losing all of your hair. Not just the hair on your head – but everywhere.

Attorney Laura Freeman of Phoenix, Arizona has been living with this kind of hair loss since she was 22. She’s among an estimated 6.8 million Americans who have alopecia areata, an autoimmune disease that starts out with small bald patches that can progress to loss of scalp and facial hair (alopecia totalis) and, in rare cases, total loss of body hair (alopecia universalis).1

For Laura, a 41-year-old mother of four young children, periodic patchy hair loss began after a bout with chicken pox when she was a toddler. “Sometimes I would have large bald spots all over my head that were impossible to conceal. Other times, they would be small and hardly noticeable,” she recalls. “Yet, I remember a constant sense of worry about it. I didn’t have hair like the other kids. I never would. Children made fun of me. I remember store clerks asking my mom if I had cancer.”

For several years, Laura tried minoxidil (Rogaine), which produced only peach fuzz hair growth and caused rashes. She also had cortisone injections into her scalp. The shots worked, but they were painful and caused thinning skin, so she was forced to abandon that approach as well.

In the summer of 1998, as she was preparing to go to law school, Laura lost her eyebrows and eyelashes and became totally bald. Her only option: wearing a wig.

“It was expensive and depressing and necessary,” Laura remarks. Her lack of eyelashes and eyebrows are especially noticeable, even with the wig. “After I got my wig, I remember telling friends who asked about it or who wondered if my hair was real. It’s still socially uncomfortable for me even at the age of 41.”

A Yale University study of almost 2,000 patients published online in July finds that alopecia areata causes a negative impact on quality of life, particularly in social functioning, psychological and emotional distress.2 “The results of this study lend further support to the fact that AA [alopecia areata] is not a ‘cosmetic’ problem but rather a medical disorder with important negative health consequences,” the study authors conclude.2

Clinical trials of three drugs FDA-approved for other autoimmune disorders may one day change that outlook for alopecia areata patients.

Roots of the Problem

Our hair follicles cycle between an active growth phase – anagen -- and a resting phase -- telogen. We normally lose 60 to 100 hairs every day, as hair is shed by follicles in telogen to make room for new growth (hair grows around a half inch each month). Excessive hair loss can be triggered by stress, pregnancy, illness, genetics (male pattern baldness, or androgenic alopecia) and autoimmunity.

In autoimmune alopecia areata, killer T-cells (cytotoxic T-lymphocytes), the shock troops of the immune system, target hair follicles. T-cell invasion doesn’t destroy the follicles and hair root, but the resulting inflammation causes the follicles to shrink, forcing them into a dormant state that dramatically slows production of hair.3 Because the follicles are still alive and hair roots are still supplied with stem cells, they have the potential to produce hair again. Indeed, in some people with alopecia areata, hair starts to grow again spontaneously.1

The trio of drugs being tested in clinical trials for alopecia block a family of enzymes called Janus kinases (JAKs) involved in inflammatory cell-signalling, the same pathway that triggers killer T-cells to attack hair follicles. Blocking JAK enzymes shuts off that signal, explains Angela M. Christiano, PhD, a professor in the Departments of Dermatology, Genetics and Development at Columbia University in New York. Dr. Christiano has a personal motivation for her research; she lost her own hair to alopecia areata in 1995 (it has since grown back).

JAK inhibitors not only appear to prevent T-cells from attacking the hair follicle but also seem to act locally, awakening dormant follicles, adds Dr. Christiano. In lab experiments with mouse and human hair follicles, her team found that JAK inhibitors could promote rapid, robust hair growth.4

In 2015, the Columbia researchers reported that the JAK inhibitor ruxolitinib restored almost complete hair growth in three individuals with longstanding and severe disease.5

“The hair follicle is one of a handful of body sites normally protected from the immune system. We call this ‘immune privilege,’” Dr. Christiano explains. T-cells violate the immune privilege of hair follicles in anagen, leading to loss of the growing hair shaft.6 “To treat it we not only need to control the immune response but also restore the immune privileged state of the hair follicle,” she adds. So far, researchers haven’t found a way to do that.

Judging the JAKs

The three JAK inhibitors being tested in alopecia areata are already in use for other disorders.

Tofacitinib (Xeljanz) is approved for rheumatoid arthritis. Ustekinumab (Stelara) is used to treat psoriatic arthritis. A third JAK inhibitor, oral ruxolitinib (Jakafi) is used to treat the bone marrow disorder myelofibrosis. Their FDA-approved status means much is known about the drugs’ safety. However, their effectiveness in alopecia areata has only been tested in small numbers of patients.

A preliminary study of three patients given ustekinumab injected under the skin (subcutaneously) was conducted at Mount Sinai Hospital in New York. Just-published results show that after 20 weeks, hair growth ranged from 25% to 85% in those patients.7 The patient with total hair loss (alopecia universalis) had the greatest amount or hair regrowth -- over 90%. The researchers also reported a decrease in inflammatory markers, and normalization of hair keratin and immune-related genes seen in scalp biopsies after 20 weeks of treatment.7 A larger study is now underway.

Another newly-published study, from researchers at Yale University, reported successful hair regrowth in a patient using topical ruxolitinib.8 A follow-up study with multiple patients is being planned.

Massachusetts-based Concert Pharmaceuticals announced in May that a modified analogue of ruxolitinib, dubbed CTP543, will start Phase 1 clinical evaluation later this year, with efficacy studies expected in 2017.9 CTP543 targets two JAK enzymes: JAK-1 and JAK-2.

As with other drugs that dampen the immune system, oral or injected JAK inhibitors can increase the risk for infection. Topical formulations designed expressly for the scalp may pose less of a risk, but high concentrations will likely be needed to produce an effect, cautions Dr. Christiano.

Larger and longer clinical trials will be needed to establish JAK inhibitors safe and effective for reversing alopecia areata.

The Genetic Connection

Dr. Christiano and her colleagues have identified approximately 14 genes that predispose people to alopecia areata. Among them are genes involved in the activation of JAK enzymes and the resulting inflammation that drives alopecia areata. Those genes are also associated with rheumatoid arthritis, thyroid disease, and celiac disease.

In fact, people with alopecia areata are at higher risk for other autoimmune problems, such as thyroid disease or vitiligo, which produces patches of light or pigment-free skin.

Genetic connections also mean people with alopecia areata are more likely to have family members with autoimmune diseases. Laura was diagnosed with Hashimoto’s thyroiditis in 2013; her mother has rheumatoid arthritis.

“I am constantly worried about taking on another autoimmune disease. I worry about my children developing autoimmune disease as well,” says Laura. “One of my daughters was having gastrointestinal issues this year. Both her gastroenterologist and allergist suggested that with my history of autoimmunity that she was at risk for a GI autoimmune disease -- Crohns, Colitis, or Celiac. So far, she has tested negative, thank goodness.”

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), loss of hair meant to protect the body can also make people vulnerable to infections and allergies. For example, your eyelashes and eyebrows are meant to keep foreign particles from getting in your eyes; hair in your nose is meant to trap dust and germs as well as foreign bodies.

Dr. Christiano is now experimenting with stem cells to promote hair growth, since these cells have the capacity to morph into any type of tissue. The idea is to inject stem cells enriched with growth factors into hair follicles. She’s formed a start-up, aptly named Rapunzel, to gather venture capital funding for the research.11

So far, Dr. Christiano and colleagues have been able to grow hair in tissue culture scaffolding in the lab.11 She hopes one day the strategy may not only help patients with alopecia areata -- but also people with hereditary hair loss.

References

1 Alopecia Areata Foundation, Alopecia Areata. https://www.naaf.org/alopecia-areata. Accessed July 28, 2016.

2 Liu LY, King BA, and Craiglow BG. Health-related quality of life (HRQoL) among patients with alopecia areata (AA): A systematic review. J Am Acad Dermatol. DOI: http://dx.doi.org/10.1016/j.jaad.2016.04.035. Published online July 16, 2016. 0190-9622. Accessed July 28.

3 Xing L, Dai Z, Jabbari A, et al., Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nature Medicine. 2014;20:1043-1049. doi:10.1038/nm.3645.

4 Harel S, Higgins CA, Cerise JE, et al., Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Science Advances. 23 Oct 2015:Vol.1, no. 9, e1500973. DOI: 10.1126/sciadv.1500973 http://advances.sciencemag.org/content/1/9/e1500973.

5 Mohammadi D, A Ray of Hope for Alopecia Areata Patients. The Pharmaceutical Journal, May 2016, Vol 296, No 7889, online | DOI:10.1211/PJ.2016.20201092. http://www.pharmaceutical-journal.com/news-and-analysis/features/finding-new-treatments-for-alopecia-areata-patients/20201092.article Accessed August 1, 2016.

6 Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clinical, Cosmetic and Investigational Dermatology. 2015; 8: 397–403. https://dx.doi.org/10.2147/CCID.S53985. Accessed July 28, 2016.

7 Guttman-Yassky E, Ungar B, Noda S, et al., Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism. J Allergy Clin Immunol. 2016;137(1):301-304. DOI: http://dx.doi.org/10.1016/j.jaci.2015.11.001

8 Craiglow BG, Daniel Tavares D, King BA. Topical Ruxolitinib for the Treatment of Alopecia Universalis. JAMA Dermatol. 2016;152(4):490-491. doi:10.1001/jamadermatol.2015.4445.

9 Concert Pharmaceuticals Unveils CTP543 for Treatment of Alopecia Areata. Business Wire, May 4, 2016. http://www.businesswire.com/news/home/20160504006458/en/Concert-Pharmaceuticals-Unveils-CTP-543-Treatment-Alopecia-Areata. Accessed August 9, 2016

10 National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Questions and Answers About Alopecia Areata. April 2015. http://www.niams.nih.gov/health_info/alopecia_areata/ Accessed July 28, 2016.

11 Keshavan M, There’s new hope for treating hair loss – in women, too. STAT News.August 12, 2016. https://www.statnews.com/2016/08/12/hair-loss-biotech-women/ Accessed August 16, 2016.

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HPV Vaccine and Women with Autoimmune Disease

August 2, 2016
Tags: Human papillomavirus, HPV vaccine, vaccines and autoimmunity, risks of infection, HPV and cervical cancer
In my first blog post on connections between cervical cancer risk and systemic lupus erythematosus, I suggested that, since high-risk strains of sexually-transmitted human papillomavirus (HPV) cause most cases of cervical cancer, young women with SLE should ask their gynecologists about the advisability of getting the HPV vaccine.

Since there have been concerns about vaccines causing autoimmunity this raises a legitimate question: Could the HPV vaccines Gardasil, Gardasil 9, or Cervarix trigger another autoimmune disease?

A number of recent studies, including a large population study from Sweden published online July 31 in the Journal of Internal Medicine, provide some reassurance.

The study examined medical records for all 70,265 girls and women ages 10 to 30 in Sweden diagnosed with at least one of 49 autoimmune diseases between 2006 and 2010, 16% of whom had received at least one dose of HPV vaccine. The researchers found no increase in new-onset autoimmune disease in the six months after immunization.1 In fact, there was a slightly reduced risk among those who got the HPV vaccine, compared to those who were not vaccinated.1

Safe -- So Far

The scientific debate over vaccines and autoimmunity has been going on for years. Some experts contend that specific adjuvants, compounds added to vaccines to enhance immune responses, can induce autoimmune disease (notably SLE), in genetically vulnerable people.2

Studies looking at the effects of two novel adjuvants in HPV vaccines found a slight, but statistically insignificant risk of autoimmunity among women immunized in randomized clinical trials compared with controls.2

Since the first HPV vaccine, Gardasil, was licensed in 2006, the Centers for Disease Control and Prevention (CDC) has tracked adverse side effects, including autoimmune diseases such as Guillain-Barré syndrome (GBS)) and multiple sclerosis.3

GBS is a rare disorder in which immune cells damage the protective myelin sheathe around nerve cells (axons), causing muscle weakness and sometimes paralysis. GBS has been linked to viral infections (most recently to Zika virus) and, in sporadic cases, immunizations.4

Speculation is that certain proteins (peptides) in viruses and bacteria may be the same, or be similar in structure to myelin, so that antibodies the immune system produces to neutralize those threats could trigger an attack on myelin.4 As we pointed out in “The Autoimmune Connection,” such reactions could be a case of molecular mimicry and may lead to different autoimmune diseases.5

Damage in GBS is limited to peripheral axons, nerve cells outside the central nervous system in the brain and spinal cord (areas affected by MS). While most people fully recover from GBS, some do experience long-term nerve damage.4

The CDC’s Vaccine Safety Datalink has monitored adverse events after HPV immunization between August 2006 and February 2012. During that period, just over 1.4 million doses of Gardasil were administered to girls and women ages 9 to 26 years old. So far, the CDC has found no cases of GBS.3

Does HPV vaccine pose any risk?

A 2013 review of data from multiple studies by the World Health Organization’s Global Advisory Committee on Vaccine Safety concludes there has been “no increase in the risk of autoimmune diseases among girls who have received HPV vaccine compared to those who have not.” Even women who were vaccinated before they knew they were pregnant suffered no more adverse outcomes compared with those who were not vaccinated, the WHO reports.6

The largest of those studies, a register-based cohort study from Sweden and Finland, included almost 1 million girls ages 10 to 17 years, around a third of whom were vaccinated against HPV. No evidence was seen of any links between HPV vaccine and autoimmune, neurological, and venous thromboembolic events (clotting in a vein).7

An observational study in the U.S. involving almost 200,000 girls and young women who had received at least 1 dose of HPV vaccine also found no increased incidence of autoimmune diseases in the vaccinated group compared those who had not been immunized.8 The incidence of MS was not significantly higher in the vaccinated group, the study showed.

A third study cited by the WHO analyzed data from 11 clinical trials involving nearly 30,000 participants 10 years and older and also found no increased risk for autoimmune diseases with Cervarix compared with controls.9

Benefits vs. Risks

This is good news, since women with autoimmune disease are especially vulnerable to vaccine-preventable infections, says Lisen Arnheim Dahlström, PhD, of the Karolinska Institute in Stockholm, senior author of the HPV vaccine study published in July.1

Patients with rheumatoid arthritis, lupus, and other autoimmune diseases have at least 2-fold greater risk of infections compared to healthy individuals, Dahlström and her co-authors note. This may not only be due to autoimmunity but also to the immunosuppressive therapies needed to control disease activity.10

For example, there have been suggestions that therapies such as methotrexate and rituximab (Rituxan) may reduce or impair responses to common vaccines, including flu shots, while tumor necrosis factor alpha (TNF-α) drugs do not.11

Some research has found “mildly impaired” immune responses to vaccines among patients on long-term immunosuppressive therapy, but a 2008 German study concluded that “postvaccination antibody titers are usually sufficient to provide protection for the majority of immunized individuals.”8 The authors of that study contend that “the accumulated data on the safety and effectiveness of vaccines warrant immunization with the majority of vaccines for patients with chronic autoimmune or rheumatic diseases.”

The CDC stresses that studies of the HPV vaccines “have followed vaccinated individuals for ten years, and show that there is no evidence of weakened protection over time.”12

The CDC recommends HPV vaccination for 11 and 12 year-old girls, and girls and women ages 13 through 26, ideally before they become sexually active,13 a guideline supported by the American College of Rheumatology.

The WHO says it “remains reassured by the safety profile of the vaccine,” but stresses the importance of continued monitoring.

As for the risk-benefit profile, the WHO concludes “allegations of harm due to vaccination based on incomplete information may lead to unnecessary harm when effective vaccines are not used.”

Issues to discuss with your doctor for sure.

References

1 Grönlund O, Herweijer E, K. Sundström K, and Arnheim-Dahlström L. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study. Journ Int Med. Early View Online, July 31, 2016. DOI: 10.1111/joim.12535

2 Orbach H, Agmon-Levin N, Zandman-Goddard G. Vaccines and autoimmune diseases of the adult. J Intern Med. 2012 Feb;271(2):193-203. doi: 10.1111/j.1365-2796.2011.02467.x.

3 Centers for Disease Control and Prevention (CDC): Frequently Asked Questions about HPV Vaccine Safety. http://www.cdc.gov/vaccinesafety/vaccines/hpv/hpv-safety-faqs.html#A6b

4 National Institute for Neurological Diseases and Stroke (NINDS). Guillain Barré Syndrome Fact Sheet. http://www.ninds.nih.gov/disorders/gbs/detail_gbs.htm

5 Baron-Faust R, Buyon JP. “The Autoimmune Connection, 2nd Edition,” 2016, McGraw-Hill, NY. Pp. 8, 26, 290, 395.

6 World Health Organization (WHO), Global Advisory Committee on Vaccine Safety, 11–12 December 2013, Geneva, Switzerland. WHO Weekly Epidemiological Record.> 2014;7(89):53–60. Online 14 February 2014. http://www.who.int/wer, retrieved August 1, 2016.

7 Arnheim-Dahlström L, et al. Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study. BMJ. 2013 9; 347.doi: http://dx.doi.org/10.1136/bmj.f5906

8 Chao C et al. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med. 2012 Feb;271(2):193-203. doi: 10.1111/j.1365-2796.2011.02467.x.

9 Descamps D, et al. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009;5(5):332-40. Epub 2009 May 20.

10 Glück T and Müller-Ladner U. Vaccination in Patients with Chronic Rheumatic or Autoimmune Diseases. Clin Infect Dis. 2008; 46(9): 1459-1465.doi: 10.1086/587063

11 Hua C, Barnetche T, Combe B, Morel J. Effect of Methotrexate, Anti–Tumor Necrosis Factor α, and Rituximab on the Immune Response to Influenza and Pneumococcal Vaccines in Patients With Rheumatoid Arthritis: A Systematic Review and MetaAnalysis. Arthritis Care & Research. 2014;66:1016–1026. doi: 10.1002/acr.22246.

12 CDC, HPV Vaccine Information for Young Women. http://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young-women.htm.

13 Kim DK, Bridges CB, Harriman KH, et al., CDC Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2016. Morbidity and Mortality Weekly Report (MMWR). February 5, 2016 / 65(4);88–90.

14 Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2015. doi:10.1002/acr.22783.ch02.

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