Single Vaccines: A Safer Option for Children with Mastocytosis

Apr 02, 2017

A Review of Parente R, Pucino V, Magliacane D, Petraroli A, Loffredo S, Marone G, et al.  Evaluation of vaccination safety in children with mastocytosis. Pediatr Allergy Immunol. 2017 Feb; 28(1):93–95. Available from http://onlinelibrary.wiley.com/doi/10.1111/pai.12647/pdf1

Pediatric vaccination is a topic rife with controversy in today’s society. This topic is of unique relevance to patients with mast cell disease, because of the potential for mast cell activation and systemic reactions with any intervention. Unfortunately, data on reactions to vaccines in patients with mast cell disorders is scarce. Yet, the most vulnerable of mast cell patients, infants and children, face exposure to vaccines soon after birth. Physicians and parents should strive to be well informed, so that they can make the safest possible decisions. This recent article published in Pediatric Allergy and Immunology highlights new data aimed at exploring this critical topic.

Vaccination in children with mastocytosis can potentially trigger mast cell degranulation, but there is little data on the incidence of vaccination-induced anaphylaxis. It is worth noting that the signs and symptoms of anaphylaxis can be subtle in children, particularly in infants.2 Two studies are cited in which anaphylaxis or other symptoms caused by mast cell activation was attributed to routine vaccines.1,3,4 The current study also cites a report of an extensive bullous (blistering) reaction following a scheduled 4-month vaccination, in a 5-month-old child with diffuse cutaneous mastocytosis (DCM).5 The vaccination included haemophilus influenzae; protein-conjugated pneumococcal vaccine; poliomyelitis vaccine; diphtheria, pertussis, and tetanus toxoid; and rotavirus vaccine:5

Within 12 hours of vaccine administration, he became colicky. A day later, he began developing blisters filled with clear fluid that became confluent…he was treated with a 5-day course of low-dose oral steroids… he recovered with no residual skin changes. Since then, he has had 2 additional episodes of blistering associated with vaccination and viral illness. These episodes have become milder after initiation of a regimen with oral and topical sodium cromolyn.5 (p95)

The reviewed study investigated vaccination-induced reactions due to mast cell activation in children with mastocytosis.1 It was conducted in Italy between 2003 and 2015, and included 72 children. The control group was comprised of siblings of these children. A reaction to vaccination was defined as “any adverse event occurring between 1 and 72 hours after the injection.”1 Four children with mastocytosis experienced adverse reactions, including bullous lesions, urticaria, and bronchospasm. These reactions did not include systemic symptoms, including anaphylaxis. However, the researchers indicate that this could be due to the study’s small sample size. No reactions were recorded among siblings/controls during the study period.

All reactions recorded occurred following the first administration of a hexavalent (combined) vaccine preparation, against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, and hepatitis B.1 Interestingly, when the same combination vaccine was administered later in life to the same children, no reactions were reported. Superallergens, defined as “viral or bacterial products that bind specifically human IgE and thus are able to activate mast cells”1, are proposed as a possible explanation. Applying this concept, the lack of reactions seen with subsequent vaccinations could potentially be due to the development of IgM or IgG after the first vaccination, capable of neutralizing the superallergens before they are able to interact with IgE.1 A complete exploration of this concept is beyond the scope of this review.

Despite the fact that this study provides no conclusive evidence that vaccine components causing mast cell activation were the cause of the observed reactions, it is very likely. This is because of the close time relationship between vaccine administration and the onset of clinical evidence of mast cell activation.1 The conclusion is made that children with mastocytosis experience higher rates of adverse reactions following the first administration of vaccine, than the general population.1 Based on their findings, the researchers recommend the following:

1) In children with diffuse cutaneous mastocytosis (DCM), it may be safer to use single vaccines, rather than polyvalent vaccines.1,5

2) Children with mastocytosis should receive their first dose of vaccine in a controlled clinical setting. Furthermore, they should be monitored for at least 2 hours after adminstration.1 Controlled clinical setting is not defined in this article, but based on other literature it is presumed to mean a clinical setting in which anaphylaxis can be recognized and promptly treated.6

3) Parents should be provided with an emergency management plan. This should contain information on recognizing the symptoms of adverse reactions, and instructions for transport of the child to the nearest emergency room. If the child has had previous episodes of anaphylaxis, instructions should also be given for the use of epinephrine.1

Similar recommendations are made by Castells and Bancova. They recommend one vaccination at each time, and report that this approach has achieved complete success with vaccinating  pediatric DCM patients.7 In most cases, vaccines are recommended for children with mastocytosis.5 Bankova et al. conclude that for children with DCM, “The use of precautions with procedures, vigilance for common triggers (infections and immunizations), and adequate premedication is essential to reduce the risk of these severe complications.”5(p96) The Mastocytosis Society website lists sample premedication protocols. Physicians should always individualize these protocols for each child.

Single vaccines given with consideration for premedication, in a controlled environment with monitoring, is the combined cautious approach recommended by these recent publications. This article is an important starting point for discussion between patients and their healthcare providers when facing decisions regarding vaccination. These recommendations raise many important questions that warrant further investigation including:

Are patients and their physicians aware of this current information?

Are single vaccines readily available to this vulnerable population?

What are the implications for patients with other mast cell disorders including mast cell activation syndrome (MCAS) and idiopathic anaphylaxis (IA), as well as patients who are being investigated for mastocytosis at the time that vaccines are due?

The recommendations therefore indicate an urgent need for more research on vaccination in patients with mast cell disorders.

 

Please see the full text of this reviewed article here. (http://onlinelibrary.wiley.com/doi/10.1111/pai.12647/pdf)

Patients should consult their physicians, or mast cell disorder specialists, when necessary, regarding considerations of any treatment or therapy change.

 The Mastocytosis Society, Inc. greatly appreciates the dedicated physicians, researchers, drug company representatives and government agencies who have been involved in mastocytosis research and drug development over the years and, in particular, the patients, along with their support systems, who have participated or will participate in the future, in the many trials and exploratory studies in the search to cure mastocytosis and other mast cell disorders.

 

Article by

Pamela Farthing RN, BA, MSc, PhD student

The Mastocytosis Society, Inc.

April 2017 

 

Edited by

Denyse Nanan, MD                                          Jennifer Frangou, MD

The Mastocytosis Society, Inc.

 

 

 

 References

  1. Parente R, Pucino V, Magliacane D, Petraroli A, Loffredo S, Marone G, et al. Evaluation of vaccination safety in children with mastocytosis. Pediatr Allergy Immunol. 2017 Feb; 28(1):93–95. Available from: http://onlinelibrary.wiley.com/doi/10.1111/pai.12647/pdf
  1. Matito A, Carter M. Cutaneous and systemic mastocytosis in children: A risk factor for anaphylaxis? Curr Allergy Asthma Rep. 2015;15(22):22-30. https://www.ncbi.nlm.nih.gov/pubmed/26139333
  1. Alvarez‐Twose I, Vañó‐Galván S, Sánchez‐Muñoz L, Morgado JM, Matito A, Torrelo A et al. Increased serum baseline tryptase levels and extensive skin involvement are predictors for the severity of mast cell activation episodes in children with mastocytosis. Allergy. 2012;67(6): 813-821. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349769/pdf/nihms362252.pdf
  1. Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy. 2008;63:226–32. https://www.ncbi.nlm.nih.gov/pubmed/18186813
  1. Bankova LG, Walter JE, Iyengar SR, Lorenzo ME, Hornick JL, Castells MC. Generalized bullous eruption after routine vaccination in a child with diffuse cutaneous mastocytosis. J Allergy Clin Immunol Pract. 2013;1(1):94–6. Available from: http://www.jaci-inpractice.org/article/S2213-2198(12)00012-8/pdf
  1. Chung EH. Vaccine allergies. Clin Exp Vaccine Res. 2014;3(1):50-57. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890451/pdf/cevr-3-50.pdf
  1. Castells MC, Bankova LG. (2016). Reply to: routine vaccinations in diffuse cutaneous mastocytosis. J Allergy Clin Immunol Prac. 4(1), 190-191. https://www.ncbi.nlm.nih.gov/pubmed/26772937
  1. Castells MC. Mastocytosis: classification, diagnosis, and clinical presentation. Allergy Asthma Proc. 2004;25:33-6. https://www.ncbi.nlm.nih.gov/pubmed/15055560