Q:

9/22/2013
I have a 77 y/o male with recurrent anaphylaxis (ICU intubated x 3 days before I evaluated him) gives h/o episodes starting 8 yrs ago, averages 1/yr of SOB, sweating, lightheaded, vomiting and diarrhea, he denies urticaria but his hands itch. Three of the last four occurred after eating hamburgers at a fast food restaurant. He denies association with stings, new meds or OTC products. He's not travelled outside of CA and denies a h/o tick bites.

Meds: Atenolol, Amlodipine, Glucosamine/Chondroitin, fish oil and Calcium.
Abnormal Labs: Tryptase elevated at 25 then 35 ng/ml.
Alpha Gal IgE elevated at 2.01kU/L
IgE=123,IgG=562, RNP Ab 134 (<100), Scl-70 Ab 171 (<100).
Bone Marrow Bx pos for elevated mast cells at 5% with abnormal chrom:46,XY, del(11)(q21q23)[3]/46,XY[17]
Chest CT showed minor lymphadenopathy LUE.
Normal values for CBCD, Comp Met Panel, C3, C4, C1 inh function, Serotonin, SPEP, Urine metanephrines and catecholamines, ESR, TSH, and UA.

After the first Tryptase and CT results I obtained a Hem/Onc consult: the pt was asymptomatic and there was no palpable lymphadenopathy (pt on prednisone) so it was recommended to follow closely. I recommended the pt avoid beef and pork, avoid beta blockers and chondroitin, he is off prednisone and asymptomatic. I obtained the second Tryptase level which was higher than the first and the BMBx was obtained.

This is a man with mastocytosis and pos titers to Alpha Gal. Final Hem/Onc recommendations are pending Tumor Board discussion.

The pt's question, and mine, is can he have a hamburger? Is there a protocol for skin testing or a food challenge for Galactose-alpha-1,3-glactose? I'm hesitant to try it, I've reviewed with the pt multiple times the recent episodes associated with eating a hamburger. Is there a safe meat for him to eat? How reliable is the Alpha Gal test? We won't consider this until after Hem/Onc helps us in treating his Mastocytosis, I was hoping you might be able to offer some guidance.

A:

Thank you for your inquiry.

First, I would mention anecdotally that we have seen one patient with mastocytosis and IgE anti-alpha-gal. It is interesting in that the diagnosis of mastocytosis was made a few years prior to finding that this patient had IgE anti-alpha-gal. He had had over 20 episodes of severe anaphylaxis which we thought were related solely to the mastocytosis until mammalian meat was eliminated from his diet based upon the detection of IgE anti-alpha-gal. It has now been approximately one year since the dietary change was instituted and he has not had an episode of anaphylaxis subsequently.

With that prelude, I will try and answer your specific questions (References 1-13):
1. Can he have a hamburger?

Patients with anaphylaxis who have IgE anti-alpha-gal should eliminate all mammalian meat from the diet. This would include beef, pork, deer, et cetera. It may be tempting for such patients to ingest meat because, for reasons unknown, episodes do not occur consistently each time mammalian meat is eaten. We are not sure of the reason, but we do know that episodes are dose-dependent. That is, the less meat one eats, the less likely an episode would occur. In addition, episodes tend to be more common when the meat eaten is fatty. That is, it would be more likely to occur to sausage than a slice of lean meat.

2. Is there a protocol for skin testing or a food challenge for Galactose-alpha-1,3-glactose?

Yes. Skin testing is usually negative using commercial tests to beef and pork, but can be positive in such cases using the prick-to-prick method employing fresh beef or pork. In addition, cetuximab can be used for testing.

In the original report, intradermal tests to meat were used, but I have no personal experience with this, and one would have to specially prepare the intradermal extract of course to perform an intradermal.

Oral challenge can also be done. As mentioned, a positive oral challenge is more likely when a fattier cut of beef (such as ribs) is used. Small amounts of meat (e.g., a strip of bacon) are oftentimes tolerated, but the equivalent of two pork sausage (about 86 grams) usually causes symptoms, and the larger the amount (such as a plate of barbecue) is associated with increased severity of reactions. As mentioned, fattier cuts are more likely to produce a reaction than lean meats (tenderloin). It should be noted that reactions are delayed, and therefore patients should remain observation for several hours. The test is performed as you would do for any graded food challenge to detect IgE mediated sensitivity (Work Group report: Oral food challenge testing: Journal of Allergy and Clinical Immunology Vol. 123, Issue 6, Supplement, Pages S365-S383, 2009).

3. How reliable is the Alpha Gal test?

We have found the commercially available test for IgE anti-alpha-gal to be extremely reliable.

I might also mention parenthetically that I did not see that you obtained an analysis for the 816V mutation in kit. If this has not been done, I would obtain this test because patients with mastocytosis who are negative for 816V have been shown to respond to tyrosine-kinase inhibitors. It is therefore an important test to obtain. There is a reasonably sensitive blood test that can be obtained if you did not obtain this test on the bone marrow biopsy.

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

References:
1. Commins SP, Satinover SM, Hosen J, et al.: Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol 2009, 123:426-433.

2. Commins SP, Kelly LA, Rönmark E, et al.: Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma. Am J Respir Crit Care Med 2012, 185:723-730.

Data is presented that show the specific IgE Ab response can contribute to total serum IgE and preliminary evidence that the alpha-gal epitope is not airborne in homes with or without cats or dogs, under conditions where large quantities of Fel d 1 and Can f 1 can be detected. The authors concluded that the association between IgE Ab and asthma relates to IgE Ab for protein allergens that are inhaled.

3. Mullins RJ, James H, Platts-Mills TA, Commins S: Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose. J Allergy Clin Immunol 2012, 129:1334-1342.e1331.

4. Van Nunen SA, O'Connor KS, Clarke LR, Boyle RX, Fernando SL: An association between tick bite reactions and red meat allergy in humans. Med J Aust 2009, 190:510-511.

5. Jacquenet S, Moneret-Vautrin DA, Bihain BE: Mammalian meat-induced anaphylaxis: clinical relevance of anti-galactose-alpha-1,3-galactose IgE confirmed by means of skin tests to cetuximab. J Allergy Clin Immunol 2009, 124:603-605.

6. Jappe U: [Update on meat allergy : α-Gal: a new epitope, a new entity?]. Hautarzt 2012, 63:299-306.

7. O'Neil BH, Allen R, Spigel DR, et al.: High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol 2007, 25:3644-3648.

8. Chung CH, Mirakhur B, Chan E, et al.: Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 2008, 358:1109-1117.

9. Galili U, Rachmilewitz EA, Peleg A, Flechner I: A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med 1984, 160:1519-1531.

10. Commins SP, James HR, Kelly LA, et al.: The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol 2011, 127:1286-1293.e1286.

This study presents data related to tick bites inducing the IgE Ab response to alpha-gal. The report is the first example of a response to an ectoparasite giving rise to an important form of food allergy.

11. Commins SP, Platts-Mills TA: Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant. J Allergy Clin Immunol 2009, 124:652-657.

12. Valent P, Akin C, Arock M, et al. Definitions, criteria and global classifications of mast cell disorders with special reference to mast cell activation syndromes: A consensus proposal. Int Archives Allergy Immunol 2012; 157:215 -225. (III, C)

13. Swerdlow SH, Campo E, Harris NL, et al. Mastocytosis (Mast cell disease). In: World Health Organization (WHO) Classification of Tumours. Vol 2. Lyon, France: IARC Press; 2008; pages 54-63. (III, C)

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology