TOPIC: MMR and ITP

Immune thrombocytopenia (ITP) is a disease with autoimmune destruction of platelets. ITP among children has been associated with viral infections and some vaccinations. We report a case of ITP after measles-mumps-rubella (MMR) vaccination in a 10-month-old male infant who presented with purpura and acute gastrointestinal bleeding. This case was successfully treated with corticosteroids and intravenous immunoglobulin. ITP is a rare complication of the MMR vaccine that physicians should be aware of.

www.ncbi.nlm.nih.gov/pubmed/25507234

Interesting article and a few points to ponder:

I have 30+ years experience in Pediatric nursing in the Philadelphia/New York area. MMR vaccine is given at 1 year (previously 15 months)in the United States. Even in the measles outbreak now the CDC has not recommended lowering the age of administration. I am not sure why it was given at 10 months; if the standard is different in other countries or if there was an outbreak or it was given in error.

I know that MMR has been associated with ITP (among other things). We give MMR at 1 yr and the booster at 4yrs. That is also the time that we send the child for routine blood work (CBC and lead level). Most young children with ITP whose care I have participated in were diagnosed due to bruising or bleeding symptoms, but I wonder whether there are cases picked up due to routine screening which was coincidentally done around the same time as the MMR administration (I would love to know the interval between administration and diagnosis). My experience is in general pediatrics though so I have seen and treated ITP it is certainly not at the volume as if I had worked with Pediatric Hematology.

Interestingly enough my daughter was diagnosed with routine lab work, I do remember her having some large bruising for at least a year prior to her diagnosis. That would somewhat line up with some of the adolescent vaccines, although it would be impossible to make an absolute correlation. Being a health care worker I am not anti- vaccine by any means, but I also wonder if I would make the same decisions if I had to do it all over again.

I like to keep informed on vaccine issues, I do a lot of continuing ed credits on the topic.

Terri:

The topic of vaccines is an interesting one, and one that definitely has two sides. While I am not totally anti-vaccine, I refuse to get them myself for the most part, although I did get a tetanus vaccine a few years ago when I had a rusty nail go into my arm.

Having autoimmune issues in my family, I've done a fair amount of research. Some of the side effects can be scary, especially anything that is permanent. The problem is that it is so hard to pin point cause and whether or not a vaccine did cause an adverse reaction, and I suspect that many cases go unreported. I once had a bad, rare reaction to Rituxan and I asked my Hemo if he was going to report it to the FDA. He said no. That blew my mind and I ended up reporting it myself. Since then I tend to believe that reactions to drugs and vaccines are vastly under-reported. Either the connection to the vaccine/drug isn't made, or the doctor doesn't bother to report it. I know how many children have come though here and the parents suspected ITP was due to the MMR. None of them were sure though, so they probably didn't get added to the statistics.

Once a person or family member has a bad reaction, they tend to view things differently and are not quite as trusting and naive as they used to be. As time goes on, I seem to be having more bad reactions to drugs, even antibiotics. I don't take the safety of any drug lightly any more. My immune system seems to be too touchy and I end up with more problems than I started with.

All of this probably puts you in an unsure position, since future vaccines for your daughter might be an issue. That would be hard. I know I'm glad that I don't have to make those decisions for my kids any more!

Sandi, I agree with you that drug and vaccine reactions are vastly under reported, I am not sure why. I can honestly say that I have not seen very many serious reactions to vaccines, but they do happen.

I am also very glad that I do not have to make these decisions anymore, other than tetanus boosters at some point my kids are done. One thing that really bothers me though is some of the way vaccines are administered. Since many of the vaccines cover multiple diseases you can be immunizing for sometimes 7 or more diseases in one visit. Many offices will put a limit on the amount of shots in one visit but I don't think they pay enough attention to what is in those shots. I really think when these combined disease vaccines are used health care and parents should be paying attention to what ones are given together. I will say that if I was vaccinating my kids again I would opt for a staggered schedule which might involve more doctors visits but would cut down on the amount of diseases a child is immunized against at one time. And I am also not in favor of the current trend of mandating flu shots, I think that it should be a choice.

In general my philosophy with medication has been if it is necessary inform yourself but not to be taken lightly. My mother has bad reactions to medications so that may influence this thinking. And now with my daughter I carefully weigh everything especially since she could need them long term, or I am not sure how it will affect her ITP. I am even not that thrilled with her need to be on BCP because at 18 you could be looking at long term use and the possible implications of that worry me. But her hemoglobin was dropping and her heavy bleeding was having a lifestyle impact so it was necessary. I am very glad that for now we are watchful waiting because all of the medications needed to treat ITP have side effects that worry me.

Terri:

I am so glad to hear you say all of that, especially the part about mixing multiple vaccines in one shot. That really worries me too and I don't know how mothers handle that these days. I would be a nervous wreck and I'd be the mom arguing for staggered vaccines like you said. There are way too many vaccines for kids these days as opposed to years ago. I'm hoping to be a grandmother someday so I do worry about it. It's unusual for someone in the medical profession to voice those concerns.

I think you're doing a great job with your daughter by weighing all the pros and cons and making informed decisions. You have to go with what you believe is best. I know how you feel about the BCP. My daughter had to take them at 15 for heavy bleeding due to what they thought were cysts bursting. Looking back, I think she was Hypothyroid back then but no one bothered to check. I didn't know enough to question it and the internet was a new thing. Anyway, even though it was a low dose pill, she became very emotional after a few months and she stopped taking them. She was crying all the time and feeling angry for no reason, so she refused to take them. The problem cleared up in time and her periods were normal. ITP can also have some clotting issues that come with it, so you have to be aware of that too, especially while on BCP. Sometimes though, you have no choice.

I'm curious what problems your mom has had with medications? You don't have to tell me if you don't want to. I'm just always interested in medication side effects.

Sandi:

My mother was always healthy and kind of had the "if it isn't broke why fix it" approach it health care. She had a lot of common sense and practical application. As she got older though changes associated with aging crept in. In Oct 2011 at 76 she was shoveling snow after a fluke snowstorm. She fell and fractured her humerus and has had numerous complications, falls and orthopedic problems since. Since she no longer drives I am with her for a lot of her appts. So I know she has problems with codiene, sulfa, Levoquin, narcotics and Lyrica. She just seems to be very sensitive to drugs and is very cautious with drugs and how they are taken. I can say though I think for the most part the medical community presents drugs as the magic bullet. Take this and your issues resolve. And some people will have that experience. But that is not true for many drugs requiring long term use (ie BP meds, cholesterol meds, asthma meds etc). If you have a reaction then another drug will take care of that until you are taking more and more drugs. Even antibiotics can cause problems so my general feeling is if you don't need it don't take it. If you do need it inform yourself and be careful. I think medications are necessary but way over prescribed...

I have also had problems with some of those meds. Lyrica was a nightmare and I got Achilles Tendonitis from Levoquin. I also can't take sulfa drugs. It seems that once a person starts to develop sensitivities, it just keeps getting worse. It is easy to get caught up in the drug cycle once a person has chronic medical problems. My drug list has grown to 9 scripts and if my doctor had her way, she'd keep adding more. I had to put an end to it for the time being. Some side effects are permanent and can cause a lot of damage.

It's a shame your mom was doing so well until that fall. My mom is in that age group and broke her hip last year. She has not bounced back and keeps getting worse. It gets really hard when they hit that stage. I'm right there with you!

I realise I'm a little late to this topic, but I was after some thoughts from the community. My 10 month old baby has ITP, diagnosed at 2 months. Although arguably in remission (if that's the correct terminology), she's at 130k at the moment. We have the MMR vaccinations coming up. I have been warned that if you've had ITP, you're more likely to get it again, and as there is a link between the vaccine - do I give her the vaccine?? I'm not sure I could go through near zero platelets again - in hospital for weeks at a time (non responsive to treatment). We've only got near normal platelet levels in the last couple of months. She's just about the learn to walk too. Thoughts?

There is a known link between the MMR and ITP. Did your baby seem to develop ITP after an MMR vaccine? I'd discuss this with her pediatrician. It may be possible to put it off for a while if you are not comfortable with it, but it's possible that she will not have a negative reaction.

I'm glad she is doing so well now.

She developed ITP after some random bug, likely from her toddler brother. So yes, it's great that she's getting better. The issue that I'm grappling with is do I give her the vaccine that may bring it back? I'm quite conflicted about the whole thing. Obviously, yes she may be fine. But with her history and the link - don't know what to do.

This is a tough question and my advice would be to really inform yourself. MMR (usually combined with Varicella as MMRV) is given after the first birthday so at least you have a little time. There is a link in between MMR and ITP. If your daughters ITP was post viral and resolving I don't know whether she would be at a higher risk for other triggers to have her ITP relapse than the general public. I would be a little concerned about the fact that there have been both measles and mumps outbreaks so you cannot count on herd immunity (every else being immune so her chance of exposure to the disease being low) as protection. I worked through a measles outbreak in the early 1990's and I would not want to see my child have measles. Also consider that if she ever did get any of the diseases though that would have the chance of causing havoc on her ITP.

If she received IVIG though as part of her treatment there is an interval between getting IVIG and MMR vaccines (I believe it is about 7-8 months). CDC has information on their website.

For me, the risk of brain damage and other effects of the diseases are more scary than ITP. So no contest. But then I've nursed the children who've had permanent brain damage from the diseases. ITP is nothing in comparison.

I have been thinking about this for my 3 year old, who is due to get his MMR booster in a month (just two months following his ITP diagnosis). For the MMR booster, it's possible to test immunity, and then not to receive the booster if the test shows an adequate response. I may try that with my son. However, I would never not vaccinate, or even mess with the schedule too much. The risk of a young kid catching a serious disease is much higher than the risk of a reaction to a vaccine, and probabilities/various degrees of confidence are all we can go by for most things in life...

An immunity test will only shows the levels for that particular day. The problem is they may drop later on.
I had a full course of Hep B vaccinations in my early days as a nurse which brought my levels up to where they should be but I have had to receive several booster doses since. The first booster was only 6 months after the full course. .

Thrombocytopenia (Page 4)
Individuals with current thrombocytopenia may develop more severe thrombocytopenia following vaccination.
In addition, individuals who experienced thrombocytopenia with the first dose of M-M-RII (or its component vaccines)
may develop thrombocytopenia with repeat doses. Serologic status may be evaluated to determine whether or not additional doses of vaccine are needed. The potential risk to benefit ratio should be carefully evaluated before considering vaccination
in such cases
(see ADVERSE REACTIONS).

ADVERSE REACTIONS
The following adverse reactions are listed in decreasing order of severity, without regard to causality,
within each body system category and have been reported during clinical trials, with use of the marketed
vaccine, or with use of monovalent or bivalent vaccine containing measles, mumps, or rubella:
Body as a Whole
Panniculitis; atypical measles; fever; syncope; headache; dizziness; malaise; irritability
.Cardiovascular System
Vasculitis.
Digestive System
Pancreatitis; diarrhea; vomiting; parotitis; nausea.
Endocrine System
Diabetes mellitus.
Hemic and Lymphatic System
Thrombocytopenia (see WARNINGS, Thrombocytopenia); purpura; regional lymphadenopathy;
leukocytosis.
Immune System
Anaphylaxis and anaphylactoid reactions have been reported as well as related phenomena such as angioneurotic
edema (including peripheral or facial edema) and bronchial spasm in individuals with or without an allergic history

Musculoskeletal System
Arthritis; arthralgia; myalgia.Arthralgia and/or arthritis (usually transient and rarely chronic), and polyneuritis are features of infection with wild-type rubella and vary in frequency and severity with age and sex, being greatest in adult females
and least in prepubertal children. This type of involvement as well as myalgia and paresthesia, have also been reported following administration of MERUVAXII
.
Chronic arthritis has been associated with wild-type rubella infection and has been related to persistent
virus and/or viral antigen isolated from body tissues. Only rarely have vaccine recipients developed chronic joint symptoms.
Following vaccination in children, reactions in joints are uncommon and generally of brief duration. In women, incidence
rates for arthritis and arthralgia are generally higher than those seen in children (children: 0-3%; women: 12-26%),{17,56,57} and the reactions tend to be more marked and of longer duration. Symptoms may persist for a matter of months or on rare occasions for years. In adolescent girls, the reactions appear to be intermediate in incidence between those seen in children
and in adult women. Even in women older than 35 years, these reactions are generally well tolerated and rarely interfere
with normal activities.
Nervous System
Encephalitis; encephalopathy; measles inclusion body encephalitis (MIBE) (see CONTRAINDICATIONS); subacute
sclerosing panencephalitis (SSPE); Guillain-Barré Syndrome (GBS); acute disseminated encephalomyelitis (ADEM);
transverse myelitis; febrile convulsions; afebrile convulsions or seizures; ataxia; polyneuritis; polyneuropathy
; ocular palsies; paresthesia.

www.merck.com/product/usa/pi_circulars/m/mmr_ii/mmr_ii_pi.pdf

Sandi, super helpful - I'm going to take this to my son's physical at the end of August and suggest that his status be tested. Seems like there's nothing to lose. If his platelet count by then is normal (one can hope?), and his immunity is low, I will probably vaccinate. If his immunity is high, perhaps we'll retest next year if necessary. (If I recall, MMR is successful the first time in 80% of cases or so, and the booster is needed to ensure "herd immunity," for which 90%+ is needed... I could be getting the numbers wrong.) Incidentally, I travel for work to countries that have had measles outbreaks recently due to people not vaccinating (e.g. France), and had my own immunity tested because i didn't want to bring M, M or R to my son; my immunity was near zero, so I received a booster last year and had no reaction whatsoever. In fact, I got over a mild cold that had been lingering, seemingly the second I got the vaccine. Go figure...

Maria - just food for thought....the MMR and Varicella (and most other vaccines) usually last 10 years or less. Since this is the case, the general population who are over the age of 15 no longer have any immunity to those diseases. You found this out yourself. There is no such thing as herd immunity. There never will be.

In 2011, there was a measles outbreak in Quebec, Canada. More than 600 people contracted measles, and the community had a 95-97% vaccine compliance rate. Knowing that, they didn't bother to try to contain it and quarantine the affected people. That was a mistake because it just kept spreading. Supposed 'herd immunity' did not protect the community whatsoever.

There is what is known as primary vaccine failure and secondary vaccine failure. Primary vaccine failure occurs when a person gets no immunological response to a vaccine. In other words, they don't work for everyone. Secondary vaccine failure is when the immunity to a vaccine wears off and eventually, they all do. Also, some disease strains have mutated and are not covered by vaccines. So again, herd immunity does not exist and never will.

Sandi, i think that's a question of how you define herd community. is it 100% fool proof? no. is it 90% fool proof? probably not. But is a population where more kids are vaccinated less likely to suffer than one where fewer kids are vaccinated? Almost certainly.
That said, there has been a debate in the literature on how to define the term:

"The term herd immunity has been used by various authors to conform to different definitions. Earlier this situation had been identified but not corrected. We propose that it should have precise meaning for which purpose a new definition is offered: "the proportion of subjects with immunity in a given population". This definition dissociates herd immunity from the indirect protection observed in the unimmunised segment of a population in which a large proportion is immunised, for which the term 'herd effect' is proposed. It is defined as: "the reduction of infection or disease in the unimmunised segment as a result of immunising a proportion of the population"."

Source: www.ncbi.nlm.nih.gov/pubmed/11078115

There is also a good explanation here: www.ovg.ox.ac.uk/news/herd-immunity-how-does-it-work

We don't know how long exactly vaccines last. Many of my friends got tested this year, because there was an outbreak in the country where I grew up. About half of them still had antibodies, over 35 years later... I didn't.

Vaccines have been one of the primary reasons why humans live longer today than they ever did in history. They're not without risks and each new vaccine should be studied carefully. But on balance, vaccines are as close as western medicine has ever come to miracles.

Well, it depends on how you look at it. There are many discrepancies.

For example, parents and grandparents are told to get the pertussis vaccine prior to the birth of a baby to prevent possible transmission of whooping cough. However, studies show that the vaccine does not prevent infection. All the vaccine does is prevent symptoms. So, grandma gets the vaccine, contracts whooping cough and ends up being an asymptomatic carrier. She doesn't know that she has whooping cough since she is symptom free and kisses the baby. This is well known but they just keep recommending it. Hmmm.

'Pertussis has reemerged as an important public health concern since current acellular pertussis vaccines (aP) replaced older whole-cell vaccines (wP). In this study, we show nonhuman primates vaccinated with aP were protected from severe symptoms but not infection and readily transmitted Bordetella pertussis to contacts. Vaccination with wP and previous infection induced a more rapid clearance compared with naïve and aP-vaccinated animals. While all groups possessed robust antibody responses, key differences in T-cell memory suggest that aP vaccination induces a suboptimal immune response that is unable to prevent infection. These data provide a plausible explanation for pertussis resurgence and suggest that attaining herd immunity will require the development of improved vaccination strategies that prevent B. pertussis colonization and transmission.

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.'

www.pnas.org/content/early/2013/11/20/1314688110

I'm not saying at all that vaccines don't carry risks, just that the benefits outweigh the risks, if we're talking about vaccines in general terms.

If we're talking about novel vaccines more specifically, they carry more risks than the well established ones, and I'm all for very rigorous testing before new medicines of any kind hit the market. I have a cousin who ended up with narcolepsy due to a brand new swine flu vaccine. I also have hundreds of friends, cousins, and acquaintances who have never had a single serious side effect (myself included) from vaccines.

In relation to your article above, the link to the original article will take the reader to a text box that indicates that the article has had a reply. In the reply, other scientist pointed out a) the strength in the methodology of the paper you cited, and b) the weaknesses in the data analysis and thus, conclusions.

The response is here: www.pnas.org/content/111/7/E716
"We modified the model of Rohani et al. (4) to examine the empirical findings of Warfel et al. (1): We assumed aP prevents disease, with variable effects on transmission. Our results are unambiguous: a model with no vaccine effect on transmission cannot reproduce the observed epidemiological patterns after vaccination (Fig. 1B). In particular, the model predicts a decline in young-infant cases if—and only if—aP blocks transmission.

The baboon model pioneered by Warfel et al. (1) is without question a game-changer, shedding light on the impact of vaccination on disease and infection. However, the view it affords is clearer with respect to immunity and pathology than with respect to transmission. We point out that the extrapolation of the possibility of transmission from vaccinated baboons in the laboratory to the probability of transmission from vaccinated humans in the population is unwarranted. More work is needed to elucidate the relative transmissibility of infections in vaccinated vs. unvaccinated hosts. The evidence adduced above suggests, however, that vaccination with aP must have a strong effect on transmission as well as disease."

Back to the topic of MMR and ITP, I do think it's a very serious concern, and as I said, I will ask about testing my son for immunity before exposing him to the booster. It's important that we can have these discussions in a nuanced way (vs the usual internet "debates"), so thank you for engaging in such a knowledgeable and thoughtful way- I hope I haven't taken the thread too far off track. Happy to continue talking and learning about vaccines on a separate thread though!

The only thing I will say is that vaccines are not safety tested properly. They do not use true placebos; they use another vaccine or vaccine adjuvants as the 'placebo'. They recently began using the word 'comparitor' instead of the word 'placebo'. Follow-up is usually limited to no more than a few days or weeks. Safety studies for drugs are far more rigorous and credible.

Good luck with your son - I hope all goes well either way!

Interesting - I'll have to ask my friend who works on "auditing" drug trials for the NIH about the differences. In my case I seem to have side effects of almost any drug I take or longer than a week, whereas I've never reacted badly to a vaccine...

And thanks... my son is still holding steady with 4 small bruises (new ones, last week's are gone) and minor bunches of petechiae where he scratches himself (these also seem to go away quickly). It doesn't seem to be getting worse, so we haven't gone in to get a count.

Yes, check it out. Vaccine manufacturer's are not held to the same standards because they have absolutely no liability. That went into affect in 1986 when the Vaccine Compensation Injury Program began. They simply cannot be sued.

I have side effects to every drug too, but I've also had a vaccine reaction to the Tetanus which is permanent and progressive. I'm sorry about your cousin. I hope he is able to control the narcolepsy.

ebm.bmj.com/content/early/2018/07/27/bmjebm-2018-111012

^^^^^ This