Background: Analphylactic reactions to cetuximab, a monoclonal antibody used in cancer therapy, were recognized in 2007 as a regional complication related to recognition of a protein epitope by IgE. This protein epitope was defined as galactose-alpha-1,3-galactose (alpha-gal), which is found in non-primate mammalian tissue. Reactivity to this epitope was also found to occur after meat consumption with manifestations including anaphylaxis, urticaria, or angioedema. Further study showed that reactivity was induced by tick bites from the Lone Star tick. Similar cases of reaction to red meat have been described in Australia in 2006, and more recently in Japan and various European countries. In our Rheumatology practices where patients often raise concerns about possible tick-borne illnesses, we have observed patients presenting with symptoms related to consumption of mammalian meat, but generally less severe, and with IgE reactivity to alpha-gal.
Objectives: We have characterized the range of presenting symptoms in our alpha-gal positive patients, and their response to dietary modification.
Methods: Patients referred to this Rheumatology practice who had known exposure or risk factors for tick exposure were tested for IgE antibodies against galactose-alpha-1,3-galactose (alpha-gal) using a standardized test administered by Viacor-IBT, and also tested for typical Rheumatologic markers, as indicated by their symptoms. Alph-gal IgE levels varied from 0.38 to >100 kU/L (normal <0.35 kU/L).
Results: 147 patients were identified as positive for alpha-gal, and were recommended to avoid mammalian meat. Followup testing and evaluation was achieved in 38 patients, along with documentation of symptoms for improvement or persistence.
Clinical manifestations, laboratory findings, and reasons for referral in symptomatic alpha-gal positive patients were diverse. Dermatologic manifestations occurred in 9 including urticarial vasculitis, serpiginous urticarial rash, purpuric rash, psoriasiform rash, nummular eczema, and subcutaneous nodules.
Arthritic manifestations varied and included monoarthritis (one patient, with negative Lyme PCR of fluid), oligoarthritis in 2 patients, inflammatory polyarthritis in 10 who did not meet criteria for a diagnosis of RA, and polyarthralgia in 22. 15 patients were diagnosed with Rheumatoid Arthritis, and 13 with Spondyloarthritis.
28 patients were referred with positive ANA tests. 25 were felt to be false positive ANAs who did not meet criteria for any connective tissue disease. Anticardiolipin antibodies were present in 4 patients.
Surprisingly only 11 patients had a history of severe reaction to mammalian meat, and only one had been previously diagnosed with mammalian meat allergy
Of the 38 patients seen in followup, 10 reported symptom improvement with mammalian meat restriction.
Conclusion: Alpha-gal reactivity from tick bites is more common than Lyme disease or other tick-borne disease in our catchment area. The patients rarely recall distinct exposure to a Lone Start tick.
Manifestations are protean, and do not correlate with alpha-gal IgE level. Some patients are shown to improve with restriction of dietary mammalian meat. Somewhat surprisingly, other patients prefer to tolerate intermittent mild symptoms to maintain current dietary patterns.
In areas where Lone Star ticks are present, and in patients with risk factors for tick exposure, alpha gal IgE reactivity should be considered and tested for as part of a “tick panel” in patients who present with symptoms of potential rheumatologic diseases.
References  Chung C, Mirakhur B, etal. 2008. NEJM358:1109. Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose
Disclosure of Interests: Don Kimpel Speakers bureau: pfizer, merck, Jeffrey Wilson: None declared, Janet Lewis: None declared
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