Background <p>Hydroxypropyl methylcellulose (HPMC) is a food additive widely used as an excipient in oral pharmaceutical formulations. While widely used in oral formulations, its potential as an ingestible allergen remains largely unrecognized.</p> Case presentation <p>A 47-year-old man developed urticaria and angioedema after ingesting an HPMC-containing product, including a dietary probiotic drink and a digestive enzyme tablet. He presented with periorbital swelling and generalized urticaria within one hour after consuming a dietary probiotic drink. Two months prior, the patient experienced generalized urticaria and facial swelling after concomitant intake of a vitamin C drink and a digestive enzyme tablet. Skin prick tests revealed positive reactions to the capsule shell of the probiotic drink and digestive enzyme tablet. HPMC was identified as a common excipient in both digestive enzyme tablet and the capsule shell of dietary probiotic drinks and intradermal tests confirmed hypersensitivity to HPMC. An oral provocation test with HPMC induced urticaria, further supporting the diagnosis.</p> Conclusions <p>This case demonstrates that HPMC can induce immediate hypersensitivity reactions via the oral route. HPMC should be considered a potential culprit in patients with unexplained recurrent allergic reactions to oral medications or dietary supplements, particularly when multiple formulations are involved.</p>