The alpha-Gal syndrome is underdiagnosed

ACTAS De mo-Sifiliog áficas 115 (2024) 116---117 LETTER TO THE EDITOR The alpha-Gal Synd ome is Unde diagnosed El sínd ome de al a-Gal es á in adiagnos icado To he Edi o , Recen ly, Fe nández de la Fuen e e al.1published an in e es ing case associa ed wi h eac ions o De macen o ma gina us ick bi e. Fo y-eigh hou s a e ick bi e he case p esen ed an indu a ed lesion a ound he bi e and a bad bounded e y hema ous edema ous plaque accompanied by a e y pain ul bila e al palpable ce ical adenopa hy, ele- a ed le els o some hepa ic enzymes and se e al peaks o low-g ade e e (37.8 ◦C). The pa ien s es ed nega i e o ick-bo ne pa hogens Ricke sia cono ii and Bo elia bu gdo e i.1Acco dingly, he pa ien was diagnosed wi h he spo ed e e g oup disease ick-bo ne lymphadenopa- hy (TIBOLA).1 The alpha-Gal synd ome (AGS) is associa ed wi h IgE an ibodies and alle gic eac ions o ick bi es, mammalian mea consump ion and pha maceu icals con aining glycan galac ose-alpha-1,3-galac ose (␣-Gal) modifica ion in p o- eins and lipids.2 --- 5 Mul iple ick species wi h di e en ␣-Gal con en a e associa ed wi h he AGS wo ldwide.6 Hominids e ol ed wi h mul iple e en s o ca as ophic selec ion including loosing he syn hesis o ␣-Gal and hus de eloping he capaci y o p oduce IgM/IgG an ibodies and ac i a e immune mechanisms in esponse o his molecule wi h p o ec i e capaci y agains pa hogens con aining o no his glycan modifica ion.2,3,7 Acco dingly, immuniza ion wi h ␣-Gal and p obio ics wi h ␣-Gal con en can bus p o ec i e immune esponses agains pa hogen in ec ion (e.g., Re . 8). Acco ding o Cen e s o Disease Con ol and P e en ion (CDC; h ps://www.cdc.go / icks/alpha-gal/index.h ml), AGS eac ions can include hi es o i chy ash, nausea o omi ing, hea bu n o indiges ion, dia hea, cough, sho ness o b ea h, o di ficul y b ea hing, d op in blood p essu e, swelling o he lips, h oa , ongue, o eye lids, dizziness o ain ness, and se e e s omach pain. The mos common symp oms include u ica ia and angioedema, espi a o y dis ess, ca dio ascula /hea disease, gas oin- es inal symp oms, dia hea, abdominal pain, eflux, and emesis.5These symp oms can be di e en om pe son- o- pe son and commonly appea 2 --- 6 h a e ea ing mea o dai y p oduc s, o a e exposu e o p oduc s con aining ␣-Gal such as gela in-coa ed medica ions.5In some cases, mo ali y is associa ed wi h AGS while some people may no ha e alle gic eac ions a e e e y exposu e o ick bi es o ␣-Gal.5In Spain, some cases ha e p esen ed anaphylaxis o ick bi es associa ed wi h an i-␣-Gal IgE an ibody le els and ick p o eins.9 Despi e ecen ad ances in he diagnosis and ea - men o AGS,4,6 ick p o eins and immune mechanisms igge ing he AGS ha e no been ully cha ac e ized,10 and only p elimina y e idence on ick alphagalac ome ha e been ecen ly published.6Fu he mo e, he a ie y in AGS symp oma ology and case- o-case di e ences oge he wi h limi ed knowledge in heal h ca e p ac i ione s and gene al popula ion makes i di ficul o diagnose and ea AGS. Conside ing hese ac s and e en i he iden ified ick species ha e no been p e iously associa ed wi h AGS, i is ecommended o cases wi h eac ions o ick bi e like he one desc ibed by Fe nández de la Fuen e e al.1 o de ail pa ien his o y and es se um an i-␣- Gal IgE an ibody le els.4Alle gy skin es ing may be also conside ed.4 No e Fo in o ma ion on AGS in Spanish: Mazuecos, L., de la Fuen e, J., Villa , M., 2023. Las ga apa as y la ale gia a la ca ne oja. No as de di ulgación del IREC No. 3. Ins i- u o de in es igación en Recu sos Cinegé icos, Ciudad Real, Espa˜ na. 4 pp. h ps://www.i ec.es/di ulgacion-cien ifica/ no a-di ulga i a-ga apa as-y-ale gia-ca ne- oja/. Funding Ou esea ch on AGS is suppo ed by Minis e io de Ciencia e Inno ación/Agencia Es a al de In es igación MCIN/AEI/10.13039/501100011033, Spain and EU-FEDER (g an BIOGAL PID2020-116761GB-I00). Conflic o in e es The au ho decla es ha he esea ch was conduc ed in he absence o any comme cial o financial ela ionships ha could be cons ued as a po en ial conflic o in e es . h ps://doi.o g/10.1016/j.ad.2023.07.018 0001-7310/© 2023 AEDV. Published by Else ie Espa˜ na, S.L.U. This is an open access a icle unde he CC BY-NC-ND license (h p:// c ea i ecommons.o g/licenses/by-nc-nd/4.0/). ACTAS De mo-Sifiliog áficas 115 (2024) 116---117 Re e ences 1. Fe nández de la Fuen e L, He e o Ruiz S, Eche e ía B. Complica ion o a ick bi e [Ga apa a complicada]. Ac as De - mosifiliog . 2023;19:S0001-7310(23)00503-3. h ps://doi.o g/ 10.1016/j.ad.2022.07.045. 2. Van Nunen SA, O’Conno KS, Cla ke LR, Boyle RX, Fe - nando SL. An associa ion be ween ick bi e eac ions and ed mea alle gy in humans. Med J Aus . 2009;190:510---1, h p://dx.doi.o g/10.5694/j.1326-5377.2009. b02533.x. 3. Galili U. E olu ion in p ima es by ‘‘Ca as ophic-selec ion’’ in e play be ween en eloped i us epidemics, mu a ed genes o enzymes syn hesizing ca bohyd a e an igens, and na - u al an i-ca bohyd a e an ibodies. Am J Phys An h opol. 2019;168:352---63, h p://dx.doi.o g/10.1002/ajpa.23745. 4. Vaz-Rod igues R, Mazuecos L, de la Fuen e J. Cu en and u u e s a egies o he diagnosis and ea men o he alpha-Gal synd ome (AGS). J As hma Alle gy. 2022;15:957---70, h p://dx.doi.o g/10.2147/JAA.S265660. 5. Macdougall JD, Thomas KO, Iweala OI. The mea o he ma e : unde s anding and managing alpha-Gal synd ome. Immuno a ge s The . 2022;11:37---54, h p://dx.doi.o g/ 10.2147/ITT.S276872. 6. Villa M, Pacheco I, Ma eos-He nández L, Cabezas-C uz A, Tabo AE, Rod íguez-Valle M. Cha ac e iza ion o ick sali a y gland and sali a alphagalac ome e eals candida e alpha- gal synd ome disease bioma ke s. Expe Re P o eomics. 2021;18:1099---116, h p://dx.doi.o g/10.1080/14789450. 2021.2018305. 7. de la Fuen e J, Con e as M. Vaccinomics: a u u e a enue o accine de elopmen agains eme ging pa hogens. Expe Re Vaccines. 2021;20:1561---9, h p://dx.doi.o g/ 10.1080/14760584.2021.1987222. 8. Pacheco I, Díaz-Sánchez S, Con e as M, Villa M, Cabezas-C uz A, Go áza C, e al. P obio ic bac e ia wi h high alpha-Gal con en p o ec zeb afish agains mycobac e iosis. Pha maceu- icals. 2021;14:635, h p://dx.doi.o g/10.3390/ph14070635. 9. Ma eos-He nández L, Villa M, Mo al A, Ga cía Rod íguez C, Al aya A ias T, de la Osa V, e al. Tick---hos conflic : immunoglobulin E an ibodies o ick p o eins in pa ien s wi h anaphylaxis o ick bi e. Onco a ge . 2017;8:20630---44, h p://dx.doi.o g/10.18632/onco a ge .15243. 10. Sha ma SR, Ka im S. Tick sali a and he alpha-Gal syn- d ome: finding a needle in a hays ack. F on Cell In ec Mic obiol. 2021;11:680264, h p://dx.doi.o g/10.3389/ cimb. 2021.680264. J. de la Fuen ea,b aSaBio, Ins i u o de In es igación en Recu sos Cinegé icos (IREC-CSIC-UCLM-JCCM), Ronda de Toledo 12, 13005 Ciudad Real, Spain bDepa men o Ve e ina y Pa hobiology, Cen e o Ve e ina y Heal h Sciences, Oklahoma S a e Uni e si y, S illwa e , OK 74078, USA E-mail add ess: jose [email p o ec ed] 117