BACKGROUND: Adult-onset asthma and periocular xanthogranuloma is an uncommon and recently described disease. Little is known about the condition because only a few case reports and series are available.OBJECTIVE/METHODS: To describe the clinical manifestations, lung physiology, and response to systemic treatment of three patients with adult-onset asthma and periocular xanthogranuloma, followed by a review of the literature.RESULTS: Three men, with an age at diagnosis ranging from 48 to 51 years, presented with right periorbital swelling, asthma and chronic rhinosinusitis. The patients’ lung physiology was consistent with airway obstruction. Diagnosis was established by periorbital biopsy. All patients received oral corticosteroids for their periorbital swelling, without significant clinical response. Two patients received oral methotrexate, with nearly complete resolution of periorbital swelling. A third patient received oral azathioprine, without clinical response. The three patients had improvement of their asthma with inhaled steroids/long-acting bronchodilator, and immunosuppressive medication.CONCLUSION: A triad consisting of periorbital swelling, asthma and chronic rhinosinusitis should raise the suspicion of adult-onset asthma and periocular xanthogranuloma. Oral methotrexate should be considered as an alternative to corticosteroids in the treatment of this disorder.