Q:

3/10/2012
I saw a 14yo boy today with Autism who is non-communicative. His mother states that at 3 years of age he had a "blood test" that showed "allergy" to formaldehyde. The test was done after he had developed hives after rolling around on new carpeting.

 

Since 3 years of age he has not received any vaccinations. He is here now because the state of Illinois says he would need to either receive the missed vaccines or have proof of sensitivity. I discussed with the mother that to my knowledge there is not now, nor has there ever been a validated blood test to test for formaldehyde. I did discuss the possibility of patch testing which is available with formaldehyde, although I am not sure how this would help the situation. 

 

My questions are :
1) are there vaccines available that do not have any formaldehyde, since this would alleviate mom's fears, and get him properly vaccinated.
2) if not, I was thinking that I would skin test him with each of the vaccines in question and then proceed with the injection as long as the skin tests are negative.
3) would the patch test be helpful?

 

One of the underlying problems is that since he is not able to communicate we would not know right away if he was having a reaction. Thank You!

A:

Thank you for your inquiry.

The situation you described in regards to your patient is certainly difficult, and unfortunately, I am not going to be able to give you a definitive approach in dealing with the issue of vaccinating this boy. However, I can give you some guidance in terms of assessing an approach, and make some suggestions to you in this regard.

First of all, clearly the history of an IgE-mediated allergy to formaldehyde is not strong based upon the brief description you gave. However, as you imply by your request for information, one simply cannot ignore this history and proceed with vaccination with total confidence. With this preamble, I will attempt to answer your questions and then suggest an approach.

Actually there is a laboratory test for IgE against formaldehyde/formalin. It is an ImmunoCap available to assay IgE anti-formaldehyde/formalin, test code: 92610E, CPT Code: 86003. You can order it at Viracor.IBT Laboratories. For your convenience, I have copied a link below to their website which lists this test. It is: http://www.viracor.com/Test-Catalog/Detail/FormaldehydeFormalin-IgE--92610E

I cannot comment on the validation of this test, but clearly there is evidence in the literature that IgE-mediated reactions to formaldehyde can exist and produce both respiratory reactions as well as contact urticaria and anaphylaxis and that in vitro tests can be useful in confirming the presence of IgE anti-formaldehyde (see abstracts copied below).

Therefore, it would not be unreasonable for you to obtain this test prior to proceeding with immunizations. Although there have been discrepancies, as you can see from looking through the references listed below, between skin testing and in vitro testing (positive in vitro tests have been reported with negative skin tests), you might also consider skin testing to any vaccine you administered that did contain formaldehyde prior to its administration. Both a negative ELISA and negative skin test would give you some reassurance that administration of the vaccine would be safe (although not definitive proof of lack of reactivity).

You can obtain a list of the excipients of all vaccines by going to the Parameter on vaccine allergy. The reference is: Kelso JM and Li JT. Adverse reactions to vaccines. Annals of Allergy 2009; 1003:S1-S16 (Table 5). You can either obtain this from the website of the annals, or through the Joint Council of Allergy, Asthma, and Immunology website.

For your convenience, I have copied below a link to the Joint Council website from which a PDF of the Parameters can be downloaded. Table 5 contains vaccines and their excipients. The link is: http://www.allergyparameters.org/file_depot/0-10000000/30000-40000/30326/folder/73825/2009Vaccines.pdf.

I agree with you that patch testing would be of no value.

In summary, one way to approach the issue is to obtain an ELISA for IgE anti-formaldehyde, and also to do skin tests to any vaccine you might want to consider. You can find appropriate concentrations for skin testing to vaccines by reviewing Wood RA, et al., "Non-irritant skin test reactions to common vaccines" in J Allergy Clin Immunol 2007 (August); Volume 120(2), pages 478-481. If your patient has no demonstrable IgE against vaccine, and skin tests are negative, as noted, this would give you some confidence to proceed with vaccinations. If you still were reluctant, you still could administer the vaccine in a graded dosage fashion as has been prescribed for influenza vaccine.

Thank you again for your inquiry and we hope this response is helpful to you.

Abstracts:
Allergy to formaldehyde
[Article in Polish]
Adamowicz Z, Doboszyńska A, Tomaszewska I, Siemieniuk A.
Source
Zakład Chorób Wewnetrznych, Centrum Leczniczo-Rehabilitacyjne i Medycyny Pracy ATTIS w Warszawie.
Abstract
The article presents a case of 56-year-old patient, female, who developed generalized urticaria following dental treatment. The wheals appeared four hours after she left the clinic. During stomatological treatment she was given parapaste, a complex drug, consisting of cinchocaine, eugenol, paraformaldehyde and glycerin. She was admitted to hospital and was treated with prednison and cetirizine. The symptoms resolved in one day and she was discharged. This was the second episode of urticarial reaction to after dental visit. In a previous case, several months earlier, she received parapaste and Scandonest, local anaesthetic. She visited an allergologist after three weeks and skin prick tests with common allergens were done. All were negative. Then the prick tests with the ingredients of parapaste were done resulting in 5 mm diameter wheal to the solution of formaldehyde. We performed RAST to formaldehyde - the result was confirming the presence of antibodies to formaldehyde in a third class. The diagnosis of sensitization to formaldehyde was made. The incidence of allergy to dental drugs was discussed.

Arerugi. 2007 Nov;56(11):1397-402.
[Type 1 allergy to formaldehyde in root canal sealant after dental treatment: two case reports and review of the literature].
[Article in Japanese]
Kijima A, Nishino H, Umeda J, Kataoka Y.
Source
Department of Dermatology, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases.
Abstract
Two cases of generalized urticaria after the dental treatment were reported. These cases had clearly positive RAST to formaldehyde, whereas skin prick testings were negative. We diagnosed them as type I allergy due to formaldehyde. Immediate type formaldehyde allergy is not widely recognized as a major allergic complication of dental treatment. Previous reports of immediate allergy to formaldehyde in dental treatment were reviewed. The characteristics are the followings, first, it tends to represent severe symptom like anaphylaxis, second, the symptom often appears a few hours later than usual cases of anaphylaxis. Allergen tests show highly positive ratio to formaldehyde RAST, whereas skin prick test often shows false negative. Assessment of specific IgE to formaldehyde is a useful and a diagnostic measurement, and is recommended in patients at risk.

J Investig Allergol Clin Immunol. 2002;12(2):130-3.
IgE-mediated urticaria from formaldehyde in a dental root canal compound.
Tas E, Pletscher M, Bircher AJ.
Source
Dept. of Dermatology, University Hospital, Basel, Switzerland.
Abstract
A patient had suffered twice from an acute urticaria after treatment with two different dental root canal compounds (RCC). Skin prick tests with the single components and formaldehyde 1%aq. were positive to formaldehyde 1%aq., but irritant with formaldehydeRCC. Specific IgE to formaldehyde were positive. Patch tests were positive to formaldehydeRCC only. In the literature 28 patients with immediate symptoms to formaldehyde containing RCC have been described.

Allergy. 2003 Nov;58(11):1210-5.
Anaphylactic reactions to formaldehyde in root canal sealant after endodontic treatment: four cases of anaphylactic shock and three of generalized urticaria.
Braun JJ, Zana H, Purohit A, Valfrey J, Scherer P, Haïkel Y, de Blay F, Pauli G.

Contact Dermatitis. 1995 Nov;33(5):353.
Contact urticaria from formaldehyde in a root-canal dental paste.
el Sayed F, Seite-Bellezza D, Sans B, Bayle-Lebey P, Marguery MC, Bazex J.

Exposure to gaseous formaldehyde induces IgE-mediated sensitization to formaldehyde in school-children
Clinical & Experimental Allergy
Volume 26, Issue 3, pages 276–280, March 1996
Summary
Background: Children attending a primary school showed symptoms such as headache, cough, rhinitis and epistaxis. Assessment of specific IgE to formaldehyde gave positive results in some children.
Objective: Was IgE-mediated sensitization as well as symptoms in children associated with formaldehyde exposure at school?
Methods: Sixty-two 8-year-old children attending three forms at a primary school were investigated. Indoor formaldehyde concentrations were measured in classrooms of both schools (one frame construction with particleboard used extensively as panelling vs a brick building) which were consecutively attended. Assessment of specific IgE to formaldehyde was done in all children. Children were transferred to a brick building and 3 months later specific IgE to formaldehyde in pupils showing initially elevated radioallergosorbent test (RAST) values reassessed. In all children symptoms were evaluated by questionnaire before and 3 months after changing school.
Results: In the school panelled with particleboard the World Health Organization (WHO) threshold for formaldehyde of 0.050 ppm was crossed in two classrooms (0.075 ppm and 0.069 ppm) whereas in one classroom 0.043 ppm was found. RAST classes of >2 were found in three children, two of them attending the classroom with 0.075 ppm formaldehyde. Elevated RAST classes of ≥1.3 were found in another 21 pupils. Thirty-eight pupils as well as 19 control children showed RAST classes in the normal range of ≤1.2. Headache, nose bleeding, rhinitis, fatigue, cough, dry nasal mucosa and burning eyes were found in the affected children. There was a good correlation between symptoms and the formaldehyde concentrations in the classrooms. However, elevated IgE levels to formaldehyde did not correlate with symptoms. Formaldehyde concentrations in the classrooms of the brick built school were 0.029 ppm, 0.023 ppm and 0.026 ppm. After transferral specific IgE to formaldehyde decreased significantly from 1.7 ± 0.5 to 1.2 ± 0.2 (P> 0.002) as did the incidence of symptoms.
Conclusion: Gaseous formaldehyde, besides its irritant action, leads to IgE-mediated sensitization. As children are more sensitive to toxic substances than adults, threshold levels for indoor formaldehyde should be reduced for children.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology